{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:07:48Z","timestamp":1764806868885,"version":"3.46.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682"],"award-info":[{"award-number":["82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682","82173703","82293682"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The widespread clinical application of paclitaxel (PTX) in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells. To systematically identify key regulators of this resistance, we conducted a genome-wide CRISPR\/Cas9 knockout screen, which revealed that cell division cycle 6 (CDC6) is a critical determinant of cell adhesion-mediated PTX resistance. Furthermore, our results illustrate that CDC6, an essential DNA replication licensing factor, functions through a pathway distinct from previously well-characterized resistance mechanisms. Genetic depletion of CDC6 considerably sensitizes cells, markedly increasing PTX-induced cell death. In addition to its established role in chromosome stability, CDC6 physically interacts with tropomodulin-3 (Tmod3) in the cytoplasmic compartment. This interaction enhances CDC6 protein stability and drives drug resistance phenotypes through the regulation of actin cytoskeleton remodeling and facilitating focal adhesion assembly. In addition, combination treatment with PTX and actin filament inhibitors synergistically enhanced the antitumor efficacy both in vitro and in vivo. Overall, our studies elucidate the mechanisms through which CDC6 functions as a key regulator of PTX resistance and provide a potential therapeutic strategy to increase PTX efficacy through the modulation of the cytoskeletal-adhesion axis.<\/jats:p>","DOI":"10.1038\/s41392-025-02490-7","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:04:00Z","timestamp":1764806640000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly"],"prefix":"10.1038","volume":"10","author":[{"given":"Yue","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huirui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiabo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojie","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxue","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxiang","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"2490_CR1","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.ctrv.2011.10.008","volume":"38","author":"TC Huang","year":"2012","unstructured":"Huang, T. C. & Campbell, T. C. Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: a meta-analysis. Cancer Treat. Rev. 38, 613\u2013617 (2012).","journal-title":"Cancer Treat. Rev."},{"key":"2490_CR2","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1186\/s13046-021-02168-2","volume":"40","author":"JH You","year":"2021","unstructured":"You, J. H., Lee, J. & Roh, J. L. PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells. J. Exp. Clin. Cancer Res. 40, 350 (2021).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2490_CR3","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.3390\/cancers7040897","volume":"7","author":"AM Barbuti","year":"2015","unstructured":"Barbuti, A. M. & Chen, Z. S. Paclitaxel through the ages of anticancer therapy: exploring its role in chemoresistance and radiation therapy. Cancers 7, 2360\u20132371 (2015).","journal-title":"Cancers"},{"key":"2490_CR4","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.biopha.2017.04.043","volume":"90","author":"X Shi","year":"2017","unstructured":"Shi, X. et al. Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line. Biomed. Pharmacother. 90, 897\u2013905 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"2490_CR5","volume":"43","author":"HA Abouzeid","year":"2025","unstructured":"Abouzeid, H. A., Kassem, L., Liu, X. & Abuelhana, A. Paclitaxel resistance in breast cancer: current challenges and recent advanced therapeutic strategies. Cancer Treat. Res. Commun. 43, 100918 (2025).","journal-title":"Cancer Treat. Res. Commun."},{"key":"2490_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0323-2","volume":"51","author":"S Yoon","year":"2019","unstructured":"Yoon, S. et al. EPHB6 mutation induces cell adhesion-mediated paclitaxel resistance via EPHA2 and CDH11 expression. Exp. Mol. Med. 51, 1\u201312 (2019).","journal-title":"Exp. Mol. Med."},{"key":"2490_CR7","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1093\/jnci\/djt210","volume":"105","author":"Y Kang","year":"2013","unstructured":"Kang, Y. et al. Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J. Natl. Cancer Inst. 105, 1485\u20131495 (2013).","journal-title":"J. Natl. Cancer Inst."},{"key":"2490_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3892\/ijmm.2024.5401","volume":"54","author":"Z Yang","year":"2024","unstructured":"Yang, Z. et al. Luteolin enhances drug chemosensitivity by downregulating the FAK\/PI3K\/AKT pathway in paclitaxel\u2011resistant esophageal squamous cell carcinoma. Int. J. Mol. Med. 54, 77 (2024).","journal-title":"Int. J. Mol. Med."},{"key":"2490_CR9","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41556-022-00886-z","volume":"24","author":"NP Chen","year":"2022","unstructured":"Chen, N. P., Aretz, J. & F\u00e4ssler, R. CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry. Nat. Cell Biol. 24, 723\u2013736 (2022).","journal-title":"Nat. Cell Biol."},{"key":"2490_CR10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/sj.embor.7400624","volume":"7","author":"E Lau","year":"2006","unstructured":"Lau, E., Zhu, C., Abraham, R. T. & Jiang, W. The functional role of Cdc6 in S-G2\/M in mammalian cells. EMBO Rep. 7, 425\u2013430 (2006).","journal-title":"EMBO Rep."},{"key":"2490_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01623-8","volume":"21","author":"F Wang","year":"2022","unstructured":"Wang, F. et al. CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma. Mol. Cancer 21, 153 (2022).","journal-title":"Mol. Cancer"},{"key":"2490_CR12","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1016\/j.molcel.2021.03.003","volume":"81","author":"M Hossain","year":"2021","unstructured":"Hossain, M., Bhalla, K. & Stillman, B. Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication. Mol. Cell 81, 1951\u20131969.e1956 (2021).","journal-title":"Mol. Cell"},{"key":"2490_CR13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.pathol.2024.09.006","volume":"57","author":"YA Kariri","year":"2024","unstructured":"Kariri, Y. A. et al. Cell division cycle 6 is an independent prognostic biomarker in breast cancer. Pathology 57, 297\u2013304 (2024).","journal-title":"Pathology"},{"key":"2490_CR14","doi-asserted-by":"publisher","first-page":"855","DOI":"10.3390\/biology12060855","volume":"12","author":"M El Dika","year":"2023","unstructured":"El Dika, M., Dudka, D., Kloc, M. & Kubiak, J. Z. CDC6 as a key inhibitory regulator of CDK1 activation dynamics and the timing of mitotic entry and progression. Biology 12, 855 (2023).","journal-title":"Biology"},{"key":"2490_CR15","doi-asserted-by":"publisher","first-page":"e0162633","DOI":"10.1371\/journal.pone.0162633","volume":"11","author":"Y He","year":"2016","unstructured":"He, Y. et al. Cell division cycle 6 promotes mitotic slippage and contributes to drug resistance in paclitaxel-treated cancer cells. PLoS ONE 11, e0162633 (2016).","journal-title":"PLoS ONE"},{"key":"2490_CR16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.mcn.2017.04.002","volume":"84","author":"KT Gray","year":"2017","unstructured":"Gray, K. T., Kostyukova, A. S. & Fath, T. Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function. Mol. Cell Neurosci. 84, 48\u201357 (2017).","journal-title":"Mol. Cell Neurosci."},{"key":"2490_CR17","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1007\/s12551-018-0481-9","volume":"10","author":"J Parreno","year":"2018","unstructured":"Parreno, J. & Fowler, V. M. Multifunctional roles of tropomodulin-3 in regulating actin dynamics. Biophys. Rev. 10, 1605\u20131615 (2018).","journal-title":"Biophys. Rev."},{"key":"2490_CR18","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1111\/j.1365-2818.2008.02057.x","volume":"231","author":"P Naumanen","year":"2008","unstructured":"Naumanen, P., Lappalainen, P. & Hotulainen, P. Mechanisms of actin stress fibre assembly. J. Microsc. 231, 446\u2013454 (2008).","journal-title":"J. Microsc."},{"key":"2490_CR19","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1083\/jcb.200209057","volume":"161","author":"RS Fischer","year":"2003","unstructured":"Fischer, R. S., Fritz-Six, K. L. & Fowler, V. M. Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility. J. Cell Biol. 161, 371\u2013380 (2003).","journal-title":"J. Cell Biol."},{"key":"2490_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6951","volume":"6","author":"CY Lim","year":"2015","unstructured":"Lim, C. Y. et al. Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling. Nat. Commun. 6, 5951 (2015).","journal-title":"Nat. Commun."},{"key":"2490_CR21","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1182\/blood-2014-09-601484","volume":"126","author":"Z Sui","year":"2015","unstructured":"Sui, Z. et al. Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis. Blood 126, 520\u2013530 (2015).","journal-title":"Blood"},{"key":"2490_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/srep29204","volume":"6","author":"YJ Jo","year":"2016","unstructured":"Jo, Y. J., Jang, W. I., Kim, N. H. & Namgoong, S. Tropomodulin-3 is essential in asymmetric division during mouse oocyte maturation. Sci. Rep. 6, 29204 (2016).","journal-title":"Sci. Rep."},{"key":"2490_CR23","first-page":"3060","volume":"41","author":"C Jin","year":"2019","unstructured":"Jin, C., Chen, Z., Shi, W. & Lian, Q. Tropomodulin 3 promotes liver cancer progression by activating the MAPK\/ERK signaling pathway. Oncol. Rep. 41, 3060\u20133068 (2019).","journal-title":"Oncol. Rep."},{"key":"2490_CR24","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1002\/mc.23083","volume":"58","author":"H Zheng","year":"2019","unstructured":"Zheng, H. et al. Tropomodulin 3 modulates EGFR-PI3K-AKT signaling to drive hepatocellular carcinoma metastasis. Mol. Carcinog. 58, 1897\u20131907 (2019).","journal-title":"Mol. Carcinog."},{"key":"2490_CR25","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s13046-022-02411-4","volume":"41","author":"B Chen","year":"2022","unstructured":"Chen, B. et al. Cleavage of tropomodulin-3 by asparagine endopeptidase promotes cancer malignancy by actin remodeling and SND1\/RhoA signaling. J. Exp. Clin. Cancer Res. 41, 209 (2022).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2490_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101171","volume":"78","author":"Z He","year":"2025","unstructured":"He, Z. et al. TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4. Drug Resist. Updat. 78, 101171 (2025).","journal-title":"Drug Resist. Updat."},{"key":"2490_CR27","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.7150\/thno.71144","volume":"12","author":"YT Chan","year":"2022","unstructured":"Chan, Y. T. et al. CRISPR-Cas9 library screening approach for anti-cancer drug discovery: overview and perspectives. Theranostics 12, 3329\u20133344 (2022).","journal-title":"Theranostics"},{"key":"2490_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29205-8","volume":"13","author":"J Joung","year":"2022","unstructured":"Joung, J. et al. CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity. Nat. Commun. 13, 1606 (2022).","journal-title":"Nat. Commun."},{"key":"2490_CR29","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","volume":"343","author":"O Shalem","year":"2014","unstructured":"Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84\u201387 (2014).","journal-title":"Science"},{"key":"2490_CR30","doi-asserted-by":"publisher","first-page":"34395","DOI":"10.18632\/oncotarget.9118","volume":"7","author":"MB Aldonza","year":"2016","unstructured":"Aldonza, M. B., Hong, J. Y., Alinsug, M. V., Song, J. & Lee, S. K. Multiplicity of acquired cross-resistance in paclitaxel-resistant cancer cells is associated with feedback control of TUBB3 via FOXO3a-mediated ABCB1 regulation. Oncotarget 7, 34395\u201334419 (2016).","journal-title":"Oncotarget"},{"key":"2490_CR31","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/mc.23435","volume":"61","author":"T Deng","year":"2022","unstructured":"Deng, T. et al. Norcantharidin promotes cancer radiosensitization through Cullin1 neddylation-mediated CDC6 protein degradation. Mol. Carcinog. 61, 812\u2013824 (2022).","journal-title":"Mol. Carcinog."},{"key":"2490_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73474-6","volume":"10","author":"Y Youn","year":"2020","unstructured":"Youn, Y., Lee, J. C., Kim, J., Kim, J. H. & Hwang, J. H. Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells. Sci. Rep. 10, 16518 (2020).","journal-title":"Sci. Rep."},{"key":"2490_CR33","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd4811","volume":"13","author":"CM Scribano","year":"2021","unstructured":"Scribano, C. M. et al. Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel. Sci. Transl. Med. 13, eabd4811 (2021).","journal-title":"Sci. Transl. Med."},{"key":"2490_CR34","doi-asserted-by":"publisher","first-page":"19742","DOI":"10.1073\/pnas.1013557107","volume":"107","author":"H Yim","year":"2010","unstructured":"Yim, H. & Erikson, R. L. Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase. Proc. Natl. Acad. Sci. USA 107, 19742\u201319747 (2010).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2490_CR35","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s10974-013-9349-6","volume":"34","author":"M Colpan","year":"2013","unstructured":"Colpan, M., Moroz, N. A. & Kostyukova, A. S. Tropomodulins and tropomyosins: working as a team. J. Muscle Res. Cell Motil. 34, 247\u2013260 (2013).","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2490_CR36","doi-asserted-by":"publisher","first-page":"6096","DOI":"10.1074\/jbc.M115.708313","volume":"291","author":"A Das","year":"2016","unstructured":"Das, A., Fischer, R. S., Pan, D. & Waterman, C. M. YAP nuclear localization in the absence of cell-cell contact is mediated by a filamentous actin-dependent, myosin II- and phospho-YAP-independent pathway during extracellular matrix mechanosensing. J. Biol. Chem. 291, 6096\u20136110 (2016).","journal-title":"J. Biol. Chem."},{"key":"2490_CR37","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.cub.2019.12.049","volume":"30","author":"R Kumari","year":"2020","unstructured":"Kumari, R. et al. Tropomodulins control the balance between protrusive and contractile structures by stabilizing actin-tropomyosin filaments. Curr. Biol. 30, 767\u2013778.e765 (2020).","journal-title":"Curr. Biol."},{"key":"2490_CR38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nrm1552","volume":"6","author":"A Ciechanover","year":"2005","unstructured":"Ciechanover, A. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat. Rev. Mol. Cell Biol. 6, 79\u201387 (2005).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2490_CR39","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.tibs.2018.06.006","volume":"43","author":"A Rauscher","year":"2018","unstructured":"Rauscher, A., Gyimesi, M., Kov\u00e1cs, M. & M\u00e1ln\u00e1si-Csizmadia, A. Targeting myosin by blebbistatin derivatives: optimization and pharmacological potential. Trends Biochem. Sci. 43, 700\u2013713 (2018).","journal-title":"Trends Biochem. Sci."},{"key":"2490_CR40","doi-asserted-by":"publisher","first-page":"15974","DOI":"10.1016\/S0021-9258(18)66662-1","volume":"261","author":"DW Goddette","year":"1986","unstructured":"Goddette, D. W. & Frieden, C. Actin polymerization. The mechanism of action of cytochalasin D. J. Biol. Chem. 261, 15974\u201315980 (1986).","journal-title":"J. Biol. Chem."},{"key":"2490_CR41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021135118","volume":"118","author":"RS Fischer","year":"2021","unstructured":"Fischer, R. S. et al. Contractility, focal adhesion orientation, and stress fiber orientation drive cancer cell polarity and migration along wavy ECM substrates. Proc. Natl. Acad. Sci. USA 118, e2021135118 (2021).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2490_CR42","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S0248-4900(00)01101-1","volume":"92","author":"V Petit","year":"2000","unstructured":"Petit, V. & Thiery, J. P. Focal adhesions: structure and dynamics. Biol. Cell 92, 477\u2013494 (2000).","journal-title":"Biol. Cell"},{"key":"2490_CR43","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/ncb1262","volume":"7","author":"EJ Ezratty","year":"2005","unstructured":"Ezratty, E. J., Partridge, M. A. & Gundersen, G. G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat. Cell Biol. 7, 581\u2013590 (2005).","journal-title":"Nat. Cell Biol."},{"key":"2490_CR44","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nrc2803","volume":"10","author":"M Kavallaris","year":"2010","unstructured":"Kavallaris, M. Microtubules and resistance to tubulin-binding agents. Nat. Rev. Cancer 10, 194\u2013204 (2010).","journal-title":"Nat. Rev. Cancer"},{"key":"2490_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2022.100881","volume":"65","author":"ER Smith","year":"2022","unstructured":"Smith, E. R., Wang, J. Q., Yang, D. H. & Xu, X. X. Paclitaxel resistance related to nuclear envelope structural sturdiness. Drug Resist. Updat. 65, 100881 (2022).","journal-title":"Drug Resist. Updat."},{"key":"2490_CR46","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2014.07.009","volume":"31","author":"I Eke","year":"2015","unstructured":"Eke, I. & Cordes, N. Focal adhesion signaling and therapy resistance in cancer. Semin. Cancer Biol. 31, 65\u201375 (2015).","journal-title":"Semin. Cancer Biol."},{"key":"2490_CR47","doi-asserted-by":"publisher","first-page":"229ra243","DOI":"10.1126\/scitranslmed.3007965","volume":"6","author":"LM Zasadil","year":"2014","unstructured":"Zasadil, L. M. et al. Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. Sci. Transl. Med. 6, 229ra243 (2014).","journal-title":"Sci. Transl. Med."},{"key":"2490_CR48","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/ijc.32900","volume":"147","author":"N Lim","year":"2020","unstructured":"Lim, N. & Townsend, P. A. Cdc6 as a novel target in cancer: Oncogenic potential, senescence and subcellular localisation. Int. J. Cancer 147, 1528\u20131534 (2020).","journal-title":"Int. J. Cancer"},{"key":"2490_CR49","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.bbcan.2018.12.007","volume":"1871","author":"X Liu","year":"2019","unstructured":"Liu, X., Chen, Y., Li, Y., Petersen, R. B. & Huang, K. Targeting mitosis exit: a brake for cancer cell proliferation. Biochim. Biophys. Acta Rev. Cancer 1871, 179\u2013191 (2019).","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"2490_CR50","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/S0960-9822(02)70714-8","volume":"6","author":"A Bershadsky","year":"1996","unstructured":"Bershadsky, A., Chausovsky, A., Becker, E., Lyubimova, A. & Geiger, B. Involvement of microtubules in the control of adhesion-dependent signal transduction. Curr. Biol. 6, 1279\u20131289 (1996).","journal-title":"Curr. Biol."},{"key":"2490_CR51","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.1083\/jcb.201802088","volume":"217","author":"MC Jones","year":"2018","unstructured":"Jones, M. C., Askari, J. A., Humphries, J. D. & Humphries, M. J. Cell adhesion is regulated by CDK1 during the cell cycle. J. Cell Biol. 217, 3203\u20133218 (2018).","journal-title":"J. Cell Biol."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02490-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02490-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02490-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:04:01Z","timestamp":1764806641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02490-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2490"],"URL":"https:\/\/doi.org\/10.1038\/s41392-025-02490-7","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"395"}}