CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of beta-catenin and E-cadherin Article

Full Text via DOI: 10.1038/s41388-019-0983-3 PMID: 31471585 Web of Science: 000509849200015
International Collaboration

Cited authors

  • He, Yaowu; Davies, Claire M.; Harrington, Brittney S.; Hellmers, Linh; Sheng, Yonghua; Broomfield, Amy; McGann, Thomas; Bastick, Kate; Zhong, Laurie; Wu, Andy; Maresh, Grace; McChesney, Shannon; Wong, Kuan Yau; Adams, Mark N.; Sullivan, Ryan C.; Palmer, James S.; Burke, Lez J.; Ewing, Adam D.; Zhang, Xin; Margolin, David; Li, Li; Lourie, Rohan; Matsika, Admire; Srinivasan, Bhuvana; McGuckin, Michael A.; Lumley, John W.; Hooper, John D.


  • Elevated CUB-domain containing protein 1 (CDCP1) is predictive of colorectal cancer (CRC) recurrence and poor patient survival. While CDCP1 expression identifies stem cell populations that mediate lung metastasis, mechanisms underlying the role of this cell surface receptor in CRC have not been defined. We sought to identify CDCP1 regulated processes in CRC using stem cell populations, enriched from primary cells and cell lines, in extensive in vitro and in vivo assays. These experiments, demonstrating that CDCP1 is functionally important in CRC tumor initiation, growth and metastasis, identified CDCP1 as a positive regulator of Wnt signaling. Detailed cell fractionation, immunoprecipitation, microscopy, and immunohistochemical analyses demonstrated that CDCP1 promotes translocation of the key regulators of Wnt signaling, beta-catenin, and E-cadherin, to the nucleus. Of functional importance, disruption of CDCP1 reduces nuclear localized, chromatin-associated beta-catenin and nuclear localized E-cadherin, increases sequestration of these proteins in cell membranes, disrupts regulation of CRC promoting genes, and reduces CRC tumor burden. Thus, disruption of CDCP1 perturbs pro-cancerous Wnt signaling including nuclear localization of beta-catenin and E-cadherin.

Publication date

  • 2020

Published in


International Standard Serial Number (ISSN)

  • 0950-9232

Start page

  • 219

End page

  • 233


  • 39


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