CUB-domain-containing protein 1 overexpression in solid cancers promotes cancer cell growth by activating Src family kinases

Oncogene
C LeroyL Alex Gaither

Abstract

The transmembrane glycoprotein, CUB (complement C1r/C1s, Uegf, Bmp1) domain-containing protein 1 (CDCP1) is overexpressed in several cancer types and is a predictor of poor prognosis for patients on standard of care therapies. Phosphorylation of CDCP1 tyrosine sites is induced upon loss of cell adhesion and is thought to be linked to metastatic potential of tumor cells. Using a tyrosine-phosphoproteomics screening approach, we characterized the phosphorylation state of CDCP1 across a panel of breast cancer cell lines. We focused on two phospho-tyrosine pTyr peptides of CDCP1, containing Tyr707 and Tyr806, which were identified in all six lines, with the human epidermal growth factor 2-positive HCC1954 cells showing a particularly high phosphorylation level. Pharmacological modulation of tyrosine phosphorylation indicated that, the Src family kinases (SFKs) were found to phosphorylate CDCP1 at Tyr707 and Tyr806 and play a critical role in CDCP1 activity. We demonstrated that CDCP1 overexpression in HEK293 cells increases global phosphotyrosine content, promotes anchorage-independent cell growth and activates several SFK members. Conversely, CDCP1 downregulation in multiple solid cancer cell lines decreased both cell growth and S...Continue Reading

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Citations

May 2, 2017·PLoS Computational Biology·Ying LiTingting Li
Feb 13, 2021·Life Science Alliance·Kentaro KajiwaraMasato Okada
Oct 14, 2019·Archives of Biochemistry and Biophysics·Zheng WuLiang Yuan

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Datasets Mentioned

BETA
HCC1954

Methods Mentioned

BETA
immunoprecipitation

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