{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:28Z","timestamp":1786977928691,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["111822"],"award-info":[{"award-number":["111822"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,9,15]]},"abstract":"<jats:p>\n                    Epithelial\u2013mesenchymal transition (EMT) is a cell plasticity process required for metastasis and chemoresistance of carcinoma cells. We report a crucial role of the signal adaptor proteins CRK and CRKL in promoting EMT and tumor aggressiveness, as well as resistance against chemotherapy in colorectal and pancreatic carcinoma. Genetic loss of either CRKL or CRK partially counteracted EMT in three independent cancer cell lines. Strikingly, complete loss of the CRK family shifted cells strongly toward the epithelial phenotype. Cells exhibited greatly increased E\u2010cadherin and grew as large, densely packed clusters, completely lacked invasiveness and the ability to undergo EMT induced by cytokines or genetic activation of SRC. Furthermore, CRK family\u2010deficiency significantly reduced cell survival, proliferation and chemoresistance, as well as ERK1\/2 phosphorylation and c\u2010MYC protein levels. In accordance, MYC\u2010target gene expression was identified as novel hallmark process positively regulated by CRK family proteins. Mechanistically, CRK proteins were identified as pivotal amplifiers of SRC\/FAK signaling at focal adhesions, mediated through a novel positive feedback loop depending on RAP1. Expression of the\n                    <jats:italic>CRK<\/jats:italic>\n                    family and the EMT regulator\n                    <jats:italic>ZEB1<\/jats:italic>\n                    was significantly correlated in samples from colorectal cancer patients, especially in invasive regions. Further, high expression of\n                    <jats:italic>CRK<\/jats:italic>\n                    family genes was significantly associated with reduced survival in locally advanced colorectal cancer, as well as in pan\u2010cancer datasets from the TCGA project. Thus, CRK family adaptor proteins are promising therapeutic targets to counteract EMT, chemoresistance, metastasis formation and minimal residual disease. As proof of concept, CRK family\u2010mediated oncogenic signaling was successfully inhibited by a peptide\u2010based inhibitor.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32955","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T03:26:50Z","timestamp":1583724410000},"page":"1715-1731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Novel role for CRK adaptor proteins as essential components of SRC\/FAK signaling for epithelial\u2013mesenchymal transition and colorectal cancer aggressiveness"],"prefix":"10.1002","volume":"147","author":[{"given":"Fabian C.","family":"Franke","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine Klinikum Rechts der Isar, Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin 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