{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:59:49Z","timestamp":1787065189303,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201706550007"],"award-info":[{"award-number":["201706550007"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["#10967"],"award-info":[{"award-number":["#10967"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Cancer Society","award":["201706550007"],"award-info":[{"award-number":["201706550007"]}]},{"name":"Dutch Cancer Society","award":["#10967"],"award-info":[{"award-number":["#10967"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia and HIF signaling drive cancer progression and therapy resistance and have been demonstrated in breast cancer. To what extent breast cancer subtypes differ in their response to hypoxia has not been resolved. Here, we show that hypoxia similarly triggers HIF1 stabilization in luminal and basal A triple negative breast cancer cells and we use high throughput targeted RNA sequencing to analyze its effects on gene expression in these subtypes. We focus on regulation of YAP\/TAZ\/TEAD targets and find overlapping as well as distinct target genes being modulated in luminal and basal A cells under hypoxia. We reveal a HIF1 mediated, basal A specific response to hypoxia by which TAZ, but not YAP, is phosphorylated at Ser89. While total YAP\/TAZ localization is not affected by hypoxia, hypoxia drives a shift of [p-TAZ(Ser89)\/p-YAP(Ser127)] from the nucleus to the cytoplasm in basal A but not luminal breast cancer cells. Cell fractionation and YAP knock-out experiments confirm cytoplasmic sequestration of TAZ(Ser89) in hypoxic basal A cells. Pharmacological and genetic interference experiments identify c-Src and CDK3 as kinases involved in such phosphorylation of TAZ at Ser89 in hypoxic basal A cells. Hypoxia attenuates growth of basal A cells and the effect of verteporfin, a disruptor of YAP\/TAZ-TEAD\u2013mediated transcription, is diminished under those conditions, while expression of a TAZ-S89A mutant does not confer basal A cells with a growth advantage under hypoxic conditions, indicating that other hypoxia regulated pathways suppressing cell growth are dominant.<\/jats:p>","DOI":"10.3390\/ijms231710119","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hypoxia Triggers TAZ Phosphorylation in Basal A Triple Negative Breast Cancer Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-266X","authenticated-orcid":false,"given":"Qiuyu","family":"Liu","sequence":"first","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8289-7189","authenticated-orcid":false,"given":"Wanda van der","family":"Stel","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9894-3239","authenticated-orcid":false,"given":"Vera E. van der","family":"Noord","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-1544","authenticated-orcid":false,"given":"Hanneke","family":"Leegwater","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bircan","family":"Coban","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Elbertse","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joannes T. M.","family":"Pruijs","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-9220","authenticated-orcid":false,"given":"Olivier J. M.","family":"B\u00e9quignon","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-1817","authenticated-orcid":false,"given":"Gerard van","family":"Westen","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-9616","authenticated-orcid":false,"given":"Sylvia E. Le","family":"D\u00e9v\u00e9dec","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-6345","authenticated-orcid":false,"given":"Erik H. J.","family":"Danen","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dju165","DOI":"10.1093\/jnci\/dju165","article-title":"How many etiological subtypes of breast cancer: Two, three, four, or more?","volume":"106","author":"Anderson","year":"2014","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4048\/jbc.2015.18.2.149","article-title":"Differences in Clinical Outcomes between Luminal A and B Type Breast Cancers according to the St. Gallen Consensus 2013","volume":"18","author":"Ahn","year":"2015","journal-title":"J. Breast Cancer"},{"key":"ref_3","first-page":"289","article-title":"The molecular profile of luminal B breast cancer","volume":"6","author":"Creighton","year":"2012","journal-title":"Biologics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1073\/pnas.0932692100","article-title":"Repeated observation of breast tumor subtypes in independent gene expression data sets","volume":"100","author":"Sorlie","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/modpathol.2010.200","article-title":"Basal-like and triple-negative breast cancers: A critical review with an emphasis on the implications for pathologists and oncologists","volume":"24","author":"Badve","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_7","first-page":"1233","article-title":"Understanding and treating triple-negative breast cancer","volume":"22","author":"Anders","year":"2008","journal-title":"Oncology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"R4","DOI":"10.1186\/bcr1636","article-title":"Basal-like grade III invasive ductal carcinoma of the breast: Patterns of metastasis and long-term survival","volume":"9","author":"Fulford","year":"2007","journal-title":"Breast Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.18632\/oncotarget.12284","article-title":"Triple-negative breast cancer: Is there a treatment on the horizon?","volume":"8","author":"Yao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41416-020-01150-7","article-title":"Metastasis: Crosstalk between tissue mechanics and tumour cell plasticity","volume":"124","author":"Coban","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_11","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"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ncb3330","article-title":"The ever-expanding role of HIF in tumour and stromal biology","volume":"18","author":"LaGory","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.molmed.2012.08.001","article-title":"Molecular mechanisms mediating metastasis of hypoxic breast cancer cells","volume":"18","author":"Semenza","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/sonc.2002.37263","article-title":"Role of angiogenesis in tumor growth and metastasis","volume":"29","author":"Folkman","year":"2002","journal-title":"Semin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1113\/JP273309","article-title":"Hypoxia and cellular metabolism in tumour pathophysiology","volume":"595","author":"Parks","year":"2017","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10555-007-9055-1","article-title":"Hypoxia in cancer: Significance and impact on clinical outcome","volume":"26","author":"Vaupel","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7987","DOI":"10.1073\/pnas.95.14.7987","article-title":"Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway","volume":"95","author":"Huang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1089\/ars.2007.1628","article-title":"Detection and characterization of tumor hypoxia using pO2 histography","volume":"9","author":"Vaupel","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1002\/cncr.11246","article-title":"Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma","volume":"97","author":"Bos","year":"2003","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/ijc.20984","article-title":"Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in breast cancer: Retrospective study in a series of 745 patients","volume":"116","author":"Dales","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.1158\/1078-0432.CCR-05-2690","article-title":"Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer","volume":"12","author":"Generali","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1158\/1078-0432.CCR-04-1068","article-title":"c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent","volume":"10","author":"Giatromanolaki","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_24","first-page":"1831","article-title":"Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer","volume":"8","author":"Schindl","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"jcs230425","DOI":"10.1242\/jcs.230425","article-title":"YAP\/TAZ functions and their regulation at a glance","volume":"133","author":"Pocaterra","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1152\/physrev.00005.2014","article-title":"The biology of YAP\/TAZ: Hippo signaling and beyond","volume":"94","author":"Piccolo","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1016\/j.bbamcr.2016.05.001","article-title":"Inhibitors of oxygen sensing prolyl hydroxylases regulate nuclear localization of the transcription factors Smad2 and YAP\/TAZ involved in CTGF synthesis","volume":"1863","author":"Preisser","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2014.07.024","article-title":"Hypoxic conditions differentially regulate TAZ and YAP in cancer cells","volume":"562","author":"Yan","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12509","DOI":"10.18632\/oncotarget.2997","article-title":"Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype","volume":"5","author":"Xiang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11768","DOI":"10.18632\/oncotarget.4190","article-title":"HIF-1\u03b1 and TAZ serve as reciprocal co-activators in human breast cancer cells","volume":"6","author":"Xiang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.tips.2017.05.002","article-title":"Reprogramming of the Tumor in the Hypoxic Niche: The Emerging Concept and Associated Therapeutic Strategies","volume":"38","author":"Qiu","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.apsb.2019.12.010","article-title":"Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): A nexus between hypoxia and cancer","volume":"10","author":"Zhao","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7259","DOI":"10.1038\/s41598-021-86664-7","article-title":"Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy","volume":"11","author":"Koedoot","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Network (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490, 61\u201370.","DOI":"10.1038\/nature11412"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.cell.2015.09.033","article-title":"Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer","volume":"163","author":"Ciriello","year":"2015","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/ncb3216","article-title":"Genome-wide association between YAP\/TAZ\/TEAD and AP-1 at enhancers drives oncogenic growth","volume":"17","author":"Zanconato","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.5483\/BMBRep.2018.51.3.015","article-title":"DNA binding partners of YAP\/TAZ","volume":"51","author":"Kim","year":"2018","journal-title":"BMB Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1101\/gr.240663.118","article-title":"Benchmark and integration of resources for the estimation of human transcription factor activities","volume":"29","author":"Holland","year":"2019","journal-title":"Genome Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"H\u00f6ffken, V., Hermann, A., Pavenst\u00e4dt, H., and Kremerskothen, J. (2021). WWC Proteins: Important Regulators of Hippo Signaling in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13020306"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119322","DOI":"10.1016\/j.lfs.2021.119322","article-title":"Emerging oncogene ATAD2: Signaling cascades and therapeutic initiatives","volume":"276","author":"Nayak","year":"2021","journal-title":"Life Sci."},{"key":"ref_41","first-page":"16","article-title":"Multifaceted regulation and functions of YAP\/TAZ in tumors (Review)","volume":"40","author":"Liu","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.5483\/BMBRep.2018.51.3.017","article-title":"Regulation of the Hippo signaling pathway by ubiquitin modification","volume":"51","author":"Kim","year":"2018","journal-title":"BMB Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1093\/emboj\/19.24.6778","article-title":"TAZ: A novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins","volume":"19","author":"Kanai","year":"2000","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18071","DOI":"10.1074\/jbc.RA118.004251","article-title":"Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) mediate cell density-dependent proinflammatory responses","volume":"293","author":"Zhang","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1101\/gad.1602907","article-title":"Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control","volume":"21","author":"Zhao","year":"2007","journal-title":"Genes Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.celrep.2017.07.032","article-title":"The Epithelial Circumferential Actin Belt Regulates YAP\/TAZ through Nucleocytoplasmic Shuttling of Merlin","volume":"20","author":"Furukawa","year":"2017","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fonc.2019.00060","article-title":"WW Domain-Containing Proteins YAP and TAZ in the Hippo Pathway as Key Regulators in Stemness Maintenance, Tissue Homeostasis, and Tumorigenesis","volume":"9","author":"Chen","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.4049\/jimmunol.2000535","article-title":"Ligation of HLA Class I Molecules Induces YAP Activation through Src in Human Endothelial Cells","volume":"205","author":"Anwar","year":"2020","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.canlet.2017.09.003","article-title":"SRC activates TAZ for intestinal tumorigenesis and regeneration","volume":"410","author":"Byun","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e105770","DOI":"10.15252\/embj.2020105770","article-title":"Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration","volume":"40","author":"Guillermin","year":"2021","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21018","DOI":"10.1038\/s41598-020-78056-0","article-title":"Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1083\/jcb.201501025","article-title":"Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway","volume":"210","author":"Kim","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1074\/jbc.RA118.004364","article-title":"SRC tyrosine kinase activates the YAP\/TAZ axis and thereby drives tumor growth and metastasis","volume":"294","author":"Lamar","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.celrep.2019.12.075","article-title":"Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP\/TAZ Activation","volume":"30","author":"Ma","year":"2020","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1073\/pnas.1610223114","article-title":"The nonreceptor tyrosine kinase c-Src attenuates SCF(\u03b2-TrCP) E3-ligase activity abrogating Taz proteasomal degradation","volume":"114","author":"Shanzer","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.stem.2017.11.001","article-title":"YAP\/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration","volume":"22","author":"Yui","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1101\/gad.304501.117","article-title":"Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics","volume":"31","author":"Foster","year":"2017","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2011.09.048","article-title":"The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells","volume":"147","author":"Cordenonsi","year":"2011","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/aac2.12011","article-title":"Contributions of Yap and Taz dysfunction to breast cancer initiation, progression, and aging-related susceptibility","volume":"1","author":"Fresques","year":"2020","journal-title":"Aging Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1242\/jcs.075796","article-title":"Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF","volume":"124","author":"Tamm","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.cell.2012.11.026","article-title":"\u03b2-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis","volume":"151","author":"Rosenbluh","year":"2012","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1101\/gad.333146.119","article-title":"CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki\/Yap\/Taz in the nucleus","volume":"34","author":"Cho","year":"2020","journal-title":"Genes Dev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yeakley, J.M., Shepard, P.J., Goyena, D.E., VanSteenhouse, H.C., McComb, J.D., and Seligmann, B.E. (2017). A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178302"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1158\/0008-5472.CAN-17-1679","article-title":"Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer","volume":"78","author":"Iorio","year":"2018","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00204-021-03160-7","article-title":"Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation","volume":"96","author":"Yang","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ng.3593","article-title":"Functional characterization of somatic mutations in cancer using network-based inference of protein activity","volume":"48","author":"Alvarez","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nmeth.2956","article-title":"TCGA-assembler: Open-source software for retrieving and processing TCGA data","volume":"11","author":"Zhu","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1038\/s41598-019-40759-4","article-title":"Co-regulated gene expression of splicing factors as drivers of cancer progression","volume":"9","author":"Koedoot","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkw1074","article-title":"The ChEMBL database in 2017","volume":"45","author":"Gaulton","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0169-7439(95)80104-H","article-title":"Polypeptide sequence property relationships in Escherichia coli based on auto cross covariances","volume":"29","author":"Wieslander","year":"1995","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13321-017-0232-0","article-title":"Beyond the hype: Deep neural networks outperform established methods using a ChEMBL bioactivity benchmark set","volume":"9","author":"Lenselink","year":"2017","journal-title":"J. Cheminform."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/cmb.2008.0173","article-title":"Interpretable numerical descriptors of amino acid space","volume":"16","author":"Georgiev","year":"2009","journal-title":"J. Comput. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1758-2946-5-41","article-title":"Benchmarking of protein descriptor sets in proteochemometric modeling (part 1): Comparative study of 13 amino acid descriptor sets","volume":"5","author":"Swier","year":"2013","journal-title":"J. Cheminform."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s11434-006-0524-7","article-title":"A new descriptor of amino acids based on the three-dimensional vector of atomic interaction field","volume":"51","author":"Zhou","year":"2006","journal-title":"Chin. Sci. Bull."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1021\/jm00390a003","article-title":"Peptide quantitative structure-activity relationships, a multivariate approach","volume":"30","author":"Hellberg","year":"1987","journal-title":"J. Med. Chem."},{"key":"ref_79","unstructured":"Krishnapuram, B., Shah, M., Smola, A., Aggarwal, C., Shen, D., and Rastogi, R. (2016, January 13\u201317). XGBoost. Proceedings of the KDD \u201816: The 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, San Francisco, CA, USA."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:10Z","timestamp":1760142190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,4]]},"references-count":79,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231710119"],"URL":"https:\/\/doi.org\/10.3390\/ijms231710119","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,4]]}}}