{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:04:03Z","timestamp":1792015443304,"version":"4.4.0"},"reference-count":130,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]},{"name":"Royal Thai Government","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]},{"name":"Helmholtz Association (Program Infection and Immunity)","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Canine histiocytic sarcoma (HS) is a rare tumor with a poor prognosis. Rapid tumor growth often causes central hypoxia and starvation, impacting tumor progression. In the present study, HS cells were cultured under hypoxia and starvation for 1 and 3 days, simulating intermediate and central tumor zones, respectively. Cells were counted at each time point, followed by RNAseq analysis. Only hypoxia significantly reduced the cell number (p &lt; 0.05). Short-term hypoxia altered 1645 differentially expressed genes (DEGs). Upregulated genes belonged to vasculature development, and downregulated genes to cell cycle processes. Short-term starvation affected 157 genes, mainly involving responses to stimuli. Prolonged hypoxia and starvation induced 1301 and 836 DEGs, respectively. Prolonged hypoxia upregulated genes mainly involved in immune responses, response to stimulus, adhesion, and angiogenesis. Prolonged starvation upregulated genes associated with signaling, adhesion, circulatory system development, and response to stimulus. Lipid metabolism and cell cycle pathways were downregulated under prolonged hypoxia and starvation, respectively. KEGG \u201cpathways in cancer\u201d were enriched under all conditions (adjusted p-values &lt; 0.05). These findings indicate that hypoxia and starvation significantly alter the expression of genes involved in tumor progression. Further studies, namely post-translational analyses, are needed to elucidate the functional impact of these changes and identify potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms26146629","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:46:33Z","timestamp":1752237993000},"page":"6629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Alterations of Canine Histiocytic Sarcoma Cells in Response to Different Stressors"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7179-0340","authenticated-orcid":false,"given":"Thanaporn","family":"Asawapattanakul","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-7523","authenticated-orcid":false,"given":"Klaus","family":"Schughart","sequence":"additional","affiliation":[{"name":"Institute of Virology M\u00fcnster, University of M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-9767","authenticated-orcid":false,"given":"Maren","family":"von K\u00f6ckritz-Blickwede","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-4409","authenticated-orcid":false,"given":"Federico","family":"Armando","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Unit of Pathology, Department of Veterinary Science, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-9445","authenticated-orcid":false,"given":"Peter","family":"Claus","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany"},{"name":"Laboratory of Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-5644","authenticated-orcid":false,"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-6868","authenticated-orcid":false,"given":"Christina","family":"Puff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1354\/vp.39-1-74","article-title":"Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs","volume":"39","author":"Affolter","year":"2002","journal-title":"Vet. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/jvim.15673","article-title":"Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs","volume":"34","author":"Toyoda","year":"2020","journal-title":"J. Vet. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/vco.12252","article-title":"Clinical prognostic factors in canine histiocytic sarcoma","volume":"15","author":"Dervisis","year":"2017","journal-title":"Vet. Comp. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/jvim.12554","article-title":"Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006\u20132012)","volume":"29","author":"Mariani","year":"2015","journal-title":"J. Vet. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1634\/theoncologist.9-90005-10","article-title":"The role of hypoxia-induced factors in tumor progression","volume":"9","author":"Vaupel","year":"2004","journal-title":"Oncologist"},{"key":"ref_6","first-page":"19","article-title":"Clinical and pre-clinical methods for quantifying tumor hypoxia","volume":"Volume 1136","author":"Gilkes","year":"2019","journal-title":"Hypoxia and Cancer Metastasis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1740-8261.2005.00065.x","article-title":"Measurement of tumor hypoxia in spontaneous canine sarcomas","volume":"46","author":"Bruehlmeier","year":"2005","journal-title":"Vet. Radiol. Ultrasound"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pi\u00f1eiro Fern\u00e1ndez, J., Luddy, K.A., Harmon, C., and O\u2019Farrelly, C. (2019). Hepatic tumor microenvironments and effects on NK cell phenotype and function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174131"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.canlet.2016.01.043","article-title":"Tumor microenvironment and therapeutic response","volume":"387","author":"Wu","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s13402-021-00602-3","article-title":"Angiogenesis as a hallmark of solid tumors-clinical perspectives","volume":"44","author":"Majidpoor","year":"2021","journal-title":"Cell. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15330338211036304","DOI":"10.1177\/15330338211036304","article-title":"Hypoxia and the tumor microenvironment","volume":"20","author":"Li","year":"2021","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shi, R., Liao, C., and Zhang, Q. (2021). Hypoxia-driven effects in cancer: Characterization, mechanisms, and therapeutic implications. Cells, 10.","DOI":"10.3390\/cells10030678"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0167-8140(97)00186-2","article-title":"Measuring hypoxia and predicting tumor radioresistance with nuclear medicine assays","volume":"46","author":"Chapman","year":"1998","journal-title":"Radiother. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2307\/3579340","article-title":"Measurement of tumor oxygenation: A comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor","volume":"147","author":"Collingridge","year":"1997","journal-title":"Radiat. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/0360-3016(95)00170-4","article-title":"Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18] fluoromisonidazole positron emission tomography","volume":"33","author":"Koh","year":"1995","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/bjc.1992.17","article-title":"Non-invasive assessment of human tumour hypoxia with 123I-iodoazomycin arabinoside: Preliminary report of a clinical study","volume":"65","author":"Parliament","year":"1992","journal-title":"Br. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20180642","DOI":"10.1259\/bjr.20180642","article-title":"Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI","volume":"92","author":"Robinson","year":"2019","journal-title":"Br. J. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/jmri.24006","article-title":"Simultaneous measurement of tissue oxygen level-dependent (TOLD) and blood oxygenation level-dependent (BOLD) effects in abdominal tissue oxygenation level studies","volume":"38","author":"Ding","year":"2013","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/jmri.25051","article-title":"Feasibility and reproducibility of BOLD and TOLD measurements in the liver with oxygen and carbogen gas challenge in healthy volunteers and patients with hepatocellular carcinoma","volume":"43","author":"Bane","year":"2016","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1476-5586(03)80024-6","article-title":"Tumor oxygen dynamics: Correlation of in vivo MRI with histological findings","volume":"5","author":"Zhao","year":"2003","journal-title":"Neoplasia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10434-999-0599-x","article-title":"Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer","volume":"6","author":"Drew","year":"1999","journal-title":"Ann. Surg. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/mrm.23014","article-title":"Dynamic contrast-enhanced-MRI of tumor hypoxia","volume":"67","author":"Egeland","year":"2012","journal-title":"Magn. Reson. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.apsb.2015.05.007","article-title":"HIF-1\u03b1 pathway: Role, regulation and intervention for cancer therapy","volume":"5","author":"Masoud","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Armando, F., Gambini, M., Corradi, A., Giudice, C., Pfankuche, V.M., Brogden, G., Attig, F., von K\u00f6ckritz-Blickwede, M., Baumg\u00e4rtner, W., and Puff, C. (2020). Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1\u03b1 Downstream Pathway Resulting in a Reduced Expression of VEGF-B in vitro. Viruses, 12.","DOI":"10.3390\/v12020200"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.2174\/1566524018666181109121849","article-title":"Role of HIF-1 in cancer progression: Novel insights. A review","volume":"18","author":"Pezzuto","year":"2018","journal-title":"Curr. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/jnci\/93.4.266","article-title":"Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects","volume":"93","author":"Hockel","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120163","DOI":"10.1016\/j.lfs.2021.120163","article-title":"The role of tumor acidification in aggressiveness, cell dissemination and treatment resistance of oral squamous cell carcinoma","volume":"288","author":"Nunes","year":"2022","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s00109-020-01959-y","article-title":"The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells","volume":"98","author":"Andreucci","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10555-019-09785-6","article-title":"Acidosis promotes tumorigenesis by activating AKT\/NF-\u03baB signaling","volume":"38","author":"Yang","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1080\/15384101.2016.1231284","article-title":"Phenotypic changes of acid-adapted cancer cells push them toward aggressiveness in their evolution in the tumor microenvironment","volume":"16","author":"Damaghi","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9932","DOI":"10.1073\/pnas.1913707117","article-title":"Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells","volume":"117","author":"Favaro","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bhowmick, T., Biswas, S., and Mukherjee, A. (2024). Cellular response during cellular starvation: A battle for cellular survivability. Cell Biochem. Funct., 42.","DOI":"10.1002\/cbf.4101"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1369\/jhc.5A6743.2005","article-title":"In Situ Detection of Starvation-induced Autophagy","volume":"54","author":"Martinet","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"702","DOI":"10.4161\/auto.6.6.12376","article-title":"Short-term fasting induces profound neuronal autophagy","volume":"6","author":"Alirezaei","year":"2010","journal-title":"Autophagy"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40170-016-0158-4","article-title":"Starving cancer from the outside and inside: Separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors","volume":"4","author":"Lashinger","year":"2016","journal-title":"Cancer Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2102057118","DOI":"10.1073\/pnas.2102057118","article-title":"Metabolic plasticity allows cancer cells to thrive under nutrient starvation","volume":"118","author":"Palm","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"a041539","DOI":"10.1101\/cshperspect.a041539","article-title":"Role of Tumor Cell Intrinsic and Host Autophagy in Cancer","volume":"14","author":"Guo","year":"2024","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/1876390101103010042","article-title":"Dying for something to eat: How cells respond to starvation","volume":"3","year":"2011","journal-title":"Open Cell Signal. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2101467","DOI":"10.1002\/advs.202101467","article-title":"Advanced cancer starvation therapy by simultaneous deprivation of lactate and glucose using a MOF nanoplatform","volume":"8","author":"Yu","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1902847","DOI":"10.1002\/advs.201902847","article-title":"Augmenting tumor-starvation therapy by cancer cell autophagy inhibition","volume":"7","author":"Yang","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8026","DOI":"10.7150\/thno.38261","article-title":"Advances in nanomedicine for cancer starvation therapy","volume":"9","author":"Yu","year":"2019","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Abou Khouzam, R., Sharda, M., Rao, S.P., Kyerewah-Kersi, S.M., Zeinelabdin, N.A., Mahmood, A.S., Nawafleh, H., Khan, M.S., Venkatesh, G.H., and Chouaib, S. (2023). Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1095419"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Scheubeck, G., Berchtold, S., Smirnow, I., Schenk, A., Beil, J., and Lauer, U.M. (2019). Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus. Viruses, 11.","DOI":"10.3390\/v11070614"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dhawan, D., Hahn, N.M., Ramos-Vara, J.A., and Knapp, D.W. (2018). Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007571"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hernandez, B., Adissu, H.A., Wei, B.-R., Michael, H.T., Merlino, G., and Simpson, R.M. (2018). Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020394"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s12276-023-00977-3","article-title":"Comparative oncology: Overcoming human cancer through companion animal studies","volume":"55","author":"Oh","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Koehler, J., Sandey, M., Prasad, N., Levy, S.A., Wang, X., and Wang, X. (2020). Differential expression of miRNAs in hypoxia (\u201cHypoxamiRs\u201d) in three canine high-grade glioma cell lines. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00104"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Schiffman, J.D., and Breen, M. (2015). Comparative oncology: What dogs and other species can teach us about humans with cancer. Philos. Trans. R. Soc. B Biol. Sci., 370.","DOI":"10.1098\/rstb.2014.0231"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cassali, G.D., Nakagaki, K.Y.R., Salvi, M., Dos Reys, M.P., Rocha, M.A.N., de Campos, C.B., Ferreira, E., Rodrigues, A.C.B., Dos Reis, D.C., and Damasceno, K.A. (2025). Canine, Feline, and Murine Mammary Tumors as a Model for Translational Research in Breast Cancer. Vet. Sci., 12.","DOI":"10.3390\/vetsci12020189"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Asada, H., Tani, A., Sakuma, H., Hirabayashi, M., Matsumoto, Y., Watanabe, K., Tsuboi, M., Yoshida, S., Harada, K., and Uchikai, T. (2023). Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35813-1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106264","DOI":"10.1016\/j.tvjl.2024.106264","article-title":"Antitumor effects of inhibitors of ERK and Akt pathways in canine histiocytic sarcoma cell lines","volume":"308","author":"Sakuma","year":"2024","journal-title":"Vet. J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sakuma, H., Tomiyasu, H., Tani, A., Goto-Koshino, Y., Bonkobara, M., and Okuda, M. (2025). Molecular Classification Based on the Gene Expression Profiles in Canine Histiocytic Sarcoma Cells. Vet. Comp. Oncol., 1\u201311.","DOI":"10.1111\/vco.13071"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1158\/0008-5472.CAN-12-4521","article-title":"Coevolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse","volume":"73","author":"Stylianopoulos","year":"2013","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-023-00903-9","article-title":"Chronic stress in solid tumor development: From mechanisms to interventions","volume":"30","author":"Yan","year":"2023","journal-title":"J. Biomed. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/nprot.2018.020","article-title":"Quantifying solid stress and elastic energy from excised or in situ tumors","volume":"13","author":"Nia","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s10237-015-0682-0","article-title":"Stress-mediated progression of solid tumors: Effect of mechanical stress on tissue oxygenation, cancer cell proliferation, and drug delivery","volume":"14","author":"Mpekris","year":"2015","journal-title":"Biomech. Model. Mechanobiol."},{"key":"ref_58","first-page":"6201","article-title":"Remarkable tolerance of tumor cells to nutrient deprivation: Possible new biochemical target for cancer therapy","volume":"60","author":"Izuishi","year":"2000","journal-title":"Cancer Res."},{"key":"ref_59","first-page":"1","article-title":"Starvation stress attenuates the miRNA-target interaction in suppressing breast cancer cell proliferation","volume":"20","author":"Zhang","year":"2020","journal-title":"BMC Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.tem.2018.01.008","article-title":"Starvation, stress resistance, and cancer","volume":"29","author":"Buono","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"124ra27","DOI":"10.1126\/scitranslmed.3003293","article-title":"Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy","volume":"4","author":"Lee","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Skopichev, V., Zharkova, M., and Alistratova, F. (2021). Oncoprotective Effect of Short-Term Hypoxic Training in Model of Ehrlich Ascites Carcinoma in Mice. KnE Life Sci., 32\u201346.","DOI":"10.18502\/kls.v0i0.8915"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2407-11-331","article-title":"Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice","volume":"11","author":"Yu","year":"2011","journal-title":"BMC Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3109\/08977194.2015.1077824","article-title":"Long-term hypoxia exposure enhanced IGFBP-3 protein synthesis and secretion resulting in cell apoptosis in H9c2 myocardial cells","volume":"33","author":"Chang","year":"2015","journal-title":"Growth Factors"},{"key":"ref_65","first-page":"42","article-title":"Effect of long-term exposure to hypoxia on the proliferation of colon cancer cells in vitro","volume":"33","author":"Yang","year":"2013","journal-title":"Tumor"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s11064-016-1868-2","article-title":"Short-term differentiation of glioblastoma stem cells induces hypoxia tolerance","volume":"41","author":"Skjellegrind","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: New dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jbm.a.36786","article-title":"Short-term hypoxia promotes vascularization in co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells","volume":"108","author":"Ma","year":"2020","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/carcin\/bgt209","article-title":"HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression","volume":"34","author":"Philip","year":"2013","journal-title":"J. Carcinog."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108497","DOI":"10.1016\/j.steroids.2019.108497","article-title":"Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer","volume":"152","author":"Johnson","year":"2019","journal-title":"Steroids"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e13175","DOI":"10.14814\/phy2.13175","article-title":"Hypoxia-induced proliferation of HeLa cells depends on epidermal growth factor receptor-mediated arginase II induction","volume":"5","author":"Setty","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bendas, G., and Lubor, B. (2012). Cancer cell adhesion and metastasis: Selectins, integrins, and the inhibitory potential of heparins. Int. J. Cell Biol., 2012.","DOI":"10.1155\/2012\/676731"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yayan, J., Franke, K.J., Berger, M., Windisch, W., and Rasche, K. (2024). Adhesion, metastasis, and inhibition of cancer cells: A comprehensive review. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-023-08920-5"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1158\/0008-5472.CAN-19-1794","article-title":"Cell adhesiveness serves as a biophysical marker for metastatic potential","volume":"80","author":"Beri","year":"2020","journal-title":"Cancer Res."},{"key":"ref_76","first-page":"177","article-title":"Cell adhesion molecules and their participation in the process of inflammation and cancerogenesis","volume":"24","author":"Lekarski","year":"2008","journal-title":"Pol. Merkur. Lek."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1002\/cam4.2163","article-title":"Effect of genetic variants in cell adhesion pathways on the biochemical recurrence in prostate cancer patients with radical prostatectomy","volume":"8","author":"Yu","year":"2019","journal-title":"Cancer Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16824","DOI":"10.1002\/jcb.28940","article-title":"Low glucose availability alters the expression of genes involved in initial adhesion of human glioblastoma cancer cell line SF767","volume":"120","author":"Aftab","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_79","first-page":"151","article-title":"Cell adhesion molecules in terms of carcinogenesis","volume":"86","author":"Lorenc","year":"2014","journal-title":"Pol. J. Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"128","DOI":"10.29089\/paom\/162205","article-title":"Cell adhesion molecules in the process of carcinogenesis and metastasis","volume":"16","author":"Kwiatkowski","year":"2009","journal-title":"Pol. Ann. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cellsig.2009.01.006","article-title":"The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis","volume":"21","author":"Paschos","year":"2009","journal-title":"Cell. Signal."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1002\/ijc.22862","article-title":"Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion","volume":"121","author":"Shukla","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"38755","DOI":"10.18632\/oncotarget.16333","article-title":"Significance of PI3K\/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.2741\/4443","article-title":"The PI3K\/AKT pathway in the pathogenesis of prostate cancer","volume":"21","author":"Chen","year":"2016","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ctrv.2003.07.007","article-title":"PI3K\/Akt signalling pathway and cancer","volume":"30","author":"Vara","year":"2004","journal-title":"Cancer Treat. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Gkotinakou, I.-M., Kechagia, E., Pazaitou-Panayiotou, K., Mylonis, I., Liakos, P., and Tsakalof, A. (2020). Calcitriol suppresses HIF-1 and HIF-2 transcriptional activity by reducing HIF-1\/2\u03b1 protein levels via a VDR-independent mechanism. Cells, 9.","DOI":"10.3390\/cells9112440"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Druker, J., Wilson, J.W., Child, F., Shakir, D., Fasanya, T., and Rocha, S. (2021). Role of Hypoxia in the Control of the Cell Cycle. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094874"},{"key":"ref_88","first-page":"7603","article-title":"Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair","volume":"61","author":"Kondo","year":"2001","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e11275","DOI":"10.7717\/peerj.11275","article-title":"Downregulation of both mismatch repair and non-homologous end-joining pathways in hypoxic brain tumour cell lines","volume":"9","author":"Cowman","year":"2021","journal-title":"PeerJ"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neo.2014.11.003","article-title":"Cycling hypoxia induces a specific amplified inflammatory phenotype in endothelial cells and enhances tumor-promoting inflammation in vivo","volume":"17","author":"Tellier","year":"2015","journal-title":"Neoplasia"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Simi\u0144ska, D., G\u0105ssowska-Dobrowolska, M., Listos, J., Gutowska, I., Chlubek, D., and Baranowska-Bosiacka, I. (2021). Chronic and cycling hypoxia: Drivers of cancer chronic inflammation through HIF-1 and NF-\u03baB activation: A review of the molecular mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910701"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev.pathmechdis.3.121806.151456","article-title":"The inflammatory response to cell death","volume":"3","author":"Rock","year":"2008","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_93","first-page":"6269","article-title":"Hypoxia induces immunogenic cell death of cancer cells by enhancing the exposure of cell surface calreticulin in an endoplasmic reticulum stress-dependent manner","volume":"18","author":"Han","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"20388","DOI":"10.1073\/pnas.0908698106","article-title":"Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome","volume":"106","author":"Iyer","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Tang, Q., Wu, S., Zhao, B., Li, Z., Zhou, Q., Yu, Y., Yang, X., Wang, R., Wang, X., and Wu, W. (2024). Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments. Biomed. Pharmacother., 178.","DOI":"10.1016\/j.biopha.2024.117257"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13045-023-01498-2","article-title":"Lipid metabolic reprogramming in tumor microenvironment: From mechanisms to therapeutics","volume":"16","author":"Jin","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Du, J., and Qin, H. (2024). Lipid metabolism dynamics in cancer stem cells: Potential targets for cancers. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1367981"},{"key":"ref_98","first-page":"29","article-title":"Glutaminase-A potential target for cancer treatment","volume":"14","author":"Anthony","year":"2024","journal-title":"Biomedicines"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Liang, J., Li, L., Li, L., Zhou, X., Zhang, Z., Huang, Y., and Xiao, X. (2023). Lipid metabolism reprogramming in head and neck cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1271505"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Farhat, E., and Weber, J.-M. (2021). Hypometabolic responses to chronic hypoxia: A potential role for membrane lipids. Metabolites, 11.","DOI":"10.3390\/metabo11080503"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Agarwala, P.K., Nie, S., Reid, G.E., and Kapoor, S. (2023). Global lipid remodelling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining plasma membrane homeostasis. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1868.","DOI":"10.1016\/j.bbalip.2023.159398"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12944-022-01693-z","article-title":"Hypoxia-Induced MIF Induces Dysregulation of Lipid Metabolism in Hep2 Laryngocarcinoma Through IL-6\/JAK-STAT Pathway","volume":"21","author":"Yang","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.phrs.2012.04.005","article-title":"ERK1\/2 MAP kinases: Structure, function, and regulation","volume":"66","author":"Roskoski","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kim, M., Choi, H.Y., Woo, J.W., Chung, Y.R., and Park, S.Y. (2021). Role of CXCL10 in the progression of in situ to invasive carcinoma of the breast. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97390-5"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cyto.2012.05.002","article-title":"CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro","volume":"59","author":"Sidahmed","year":"2012","journal-title":"Cytokine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1182\/blood.V97.3.601","article-title":"Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) \u03b1\u03b2+CD8+ single-positive T cells, TCR\u03b3\u03b4+T cells, and natural killer\u2013type cells in human thymus","volume":"97","author":"Romagnani","year":"2001","journal-title":"Blood"},{"key":"ref_107","first-page":"1","article-title":"SELE gene as a characteristic prognostic biomarker of colorectal cancer","volume":"49","author":"Li","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Huang, H., Zhou, W., Chen, R., Xiang, B., Zhou, S., and Lan, L. (2021). CXCL10 is a Tumor Microenvironment and Immune Infiltration Related Prognostic Biomarker in Pancreatic Adenocarcinoma. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.611508"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1158\/1535-7163.MCT-23-0461","article-title":"Characteristics of Carcinoembryonic Antigen-Related Cell Adhesion Molecules and Their Relationship to Cancer","volume":"23","author":"Ma","year":"2024","journal-title":"Mol. Cancer Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1091\/mbc.E16-01-0058","article-title":"Roles for E-cadherin cell surface regulation in cancer","volume":"27","author":"Petrova","year":"2016","journal-title":"Mol. Biol. Cell."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9332","DOI":"10.1111\/jcmm.15585","article-title":"Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro","volume":"24","author":"Armando","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1158\/0008-5472.CAN-08-0987","article-title":"The Role of Tumor Cell\u2013Derived Connective Tissue Growth Factor (CTGF\/CCN2) in Pancreatic Tumor Growth","volume":"69","author":"Bennewith","year":"2009","journal-title":"Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12079-016-0347-5","article-title":"A potential role for CCN2\/CTGF in aggressive colorectal cancer","volume":"10","author":"Ubink","year":"2016","journal-title":"J. Cell Commun. Signal."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"66316","DOI":"10.18632\/oncotarget.19987","article-title":"Targeting of CCN2 suppresses tumor progression and improves chemo-sensitivity in urothelial bladder cancer","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"108578","DOI":"10.1016\/j.pharmthera.2023.108578","article-title":"Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases","volume":"253","author":"Isshiki","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1096\/fj.202000240RR","article-title":"Blocking CTGF\/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injury","volume":"34","author":"Barbe","year":"2020","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Resovi, A., Borsotti, P., Ceruti, T., Passoni, A., Zucchetti, M., Berndt, A., Riser, B.L., Taraboletti, G., and Belotti, D. (2020). CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy. Cells, 9.","DOI":"10.3390\/cells9040952"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1158\/1541-7786.MCR-21-0924","article-title":"TGF-\u03b2-Induced FLRT3 Attenuation Is Essential for Cancer-Associated Fibroblast\u2013Mediated Epithelial\u2013Mesenchymal Transition in Colorectal Cancer","volume":"20","author":"Yang","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Adamczyk-Gruszka, O., Horecka-Lewitowicz, A., Gruszka, J., Wawszczak-Kasza, M., Strzelecka, A., and Lewitowicz, P. (2022). FGFR-2 and Epithelial\u2013Mesenchymal Transition in Endometrial Cancer. J. Clin. Med., 11.","DOI":"10.3390\/jcm11185416"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.tvjl.2008.03.026","article-title":"Influence of persistent canine distemper virus infection on expression of RECK, matrix-metalloproteinases and their inhibitors in a canine macrophage\/monocytic tumour cell line (DH82)","volume":"182","author":"Puff","year":"2009","journal-title":"Vet. J."},{"key":"ref_121","unstructured":"(2024, May 15). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_122","unstructured":"(2024, May 15). TrimGalore: A Wrapper Around Cutadapt and FastQC to Consistently Apply Adapter and Quality Trimming to FastQ Files, with Extra Functionality for RRBS Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/trim_galore\/."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11.14.1","DOI":"10.1002\/0471250953.bi1114s51","article-title":"Mapping RNA-seq reads with STAR","volume":"51","author":"Dobin","year":"2015","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_125","first-page":"417","article-title":"iDEP Web Application for RNA-Seq Data Analysis","volume":"Volume 2284","author":"Picardi","year":"2021","journal-title":"RNA Bioinformatics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-018-2486-6","article-title":"iDEP: An integrated web application for differential expression and pathway analysis of RNA-Seq data","volume":"19","author":"Ge","year":"2018","journal-title":"BMC Bioinform."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2003-4-9-r60","article-title":"DAVID: Database for annotation, visualization, and integrated discovery","volume":"4","author":"Dennis","year":"2003","journal-title":"Genome Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"D562","DOI":"10.1093\/nar\/gki022","article-title":"NCBI GEO: Mining millions of expression profiles\u2014Database and tools","volume":"33","author":"Barrett","year":"2005","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:08:00Z","timestamp":1760033280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":130,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146629"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146629","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}