Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
- PMID: 29447112
- DOI: 10.1515/hsz-2017-0308
Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
Abstract
The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that disrupt membrane localization of CDCP1 cleaving serine proteases may interfere with the cancer promoting effects of CDCP1 proteolysis.
Keywords: CDCP1; CUB domain containing protein 1; cancer; serine protease.
Similar articles
-
Proteolysis-induced N-terminal ectodomain shedding of the integral membrane glycoprotein CUB domain-containing protein 1 (CDCP1) is accompanied by tyrosine phosphorylation of its C-terminal domain and recruitment of Src and PKCdelta.J Biol Chem. 2010 Aug 20;285(34):26162-73. doi: 10.1074/jbc.M109.096453. Epub 2010 Jun 15. J Biol Chem. 2010. PMID: 20551327 Free PMC article.
-
In vivo cleaved CDCP1 promotes early tumor dissemination via complexing with activated β1 integrin and induction of FAK/PI3K/Akt motility signaling.Oncogene. 2014 Jan 9;33(2):255-68. doi: 10.1038/onc.2012.547. Epub 2012 Dec 3. Oncogene. 2014. PMID: 23208492 Free PMC article.
-
Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.Oncogene. 2016 Jan 28;35(4):468-78. doi: 10.1038/onc.2015.101. Epub 2015 Apr 20. Oncogene. 2016. PMID: 25893298
-
Roles of CUB domain-containing protein 1 signaling in cancer invasion and metastasis.Cancer Sci. 2011 Nov;102(11):1943-8. doi: 10.1111/j.1349-7006.2011.02052.x. Epub 2011 Sep 6. Cancer Sci. 2011. PMID: 21812858 Review.
-
The role of CDCP1 (CUB domain-containing protein 1) and ADAM12 (a disintegrin and metalloproteinase 12) in ovarian cancer.J BUON. 2015 May-Jun;20(3):673-9. J BUON. 2015. PMID: 26214617 Review.
Cited by
-
Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer.Theranostics. 2020 Jan 12;10(5):2095-2114. doi: 10.7150/thno.30736. eCollection 2020. Theranostics. 2020. PMID: 32104500 Free PMC article.
-
Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1.Nat Chem Biol. 2021 Jul;17(7):776-783. doi: 10.1038/s41589-021-00783-w. Epub 2021 Apr 15. Nat Chem Biol. 2021. PMID: 33859413
-
Effective targeting of intact and proteolysed CDCP1 for imaging and treatment of pancreatic ductal adenocarcinoma.Theranostics. 2020 Mar 4;10(9):4116-4133. doi: 10.7150/thno.43589. eCollection 2020. Theranostics. 2020. PMID: 32226543 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous