CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo.
Details
Serval ID
serval:BIB_C86E2E217091
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo.
Journal
The Journal of clinical investigation
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
01/05/2020
Peer-reviewed
Oui
Volume
130
Number
5
Pages
2435-2450
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti-CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.
Keywords
Animals, Antigens, Neoplasm/biosynthesis, Antigens, Neoplasm/genetics, Benzamides, Cell Adhesion Molecules/biosynthesis, Cell Adhesion Molecules/genetics, Cell Line, Tumor, Drosophila melanogaster, Gene Expression Regulation, Neoplastic, Humans, Liposomes, MAP Kinase Signaling System, Male, Nitriles, PTEN Phosphohydrolase/biosynthesis, PTEN Phosphohydrolase/genetics, Phenylthiohydantoin/analogs & derivatives, Phenylthiohydantoin/pharmacology, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Up-Regulation, Oncology, Prostate cancer
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2021 11:40
Last modification date
19/12/2023 8:12