Apoptosis of estrogen‐receptor negative breast cancer and colon cancer cell lines by PTPα and src RNAi

Abstract

We show that siRNA-mediated suppression of protein tyrosine phosphatase a (PTPa) reduces Src activity 2 to 4-fold in breast, colon and other human cancer cell lines. Src and PTPa RNAi induced apoptosis in estrogen receptor (ER)-negative breast cancer and colon cancer cells, but not in immortalized noncancerous breast cells, ER-positive breast cancer cells or other cancer cell types tested. RNAi of other Src family members (Fyn and Yes) or of PTP1B, a phosphatase previously suggested to be an activator of Src in breast cancer, had no effect. Although further tests with primary tumor tissues are required, the unexpected correlation between ER status and Src/PTPa dependence in breast cancer cell lines may be important for planning therapeutic strategies, and the insensitivity of normal breast cells to the RNAi highlights the potential of PTPa, which may be easier to target than Src, as a therapeutic target in ER-negative breast cancer.

Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells

“…(ER)-negative MDA-MB-231 breast cancer cells, but not in MCF-7 cells (58). This suggests a differential involvement of PTP␣ and PTP⑀ in the growth control of distinct human breast cancer cell types.…”

Receptor Protein-tyrosine Phosphatase α Regulates Focal Adhesion Kinase Phosphorylation and ErbB2 Oncoprotein-mediated Mammary Epithelial Cell Motility

“…For siRNA studies, knockdowns were performed with specified siRNAs (si␣-1, 5Ј-CAGAUGGUGCAAACCGAUA dTdT-3Ј; si␣-2, 5Ј-AAGCUGGGAGCCAUUCCAAUU dTdT-3Ј) using Lipofectamine as described (34). To quantitate cell motility, 100,000 cells were seeded on the inserts.…”

“…Substrate-trapping mutant forms of PTP␣, PTP␣D1 DA , and PTP␣D2 EA (Fig. 3A) were then utilized to identify potential physiological substrates of the PTP, as described previously (34). Proteins involved in ErbB2 signaling and cell migration were tested as potential interacting partners of PTP␣(WT), PTP␣(D1 DA ), or PTP␣(D2 EA ).…”

Src family tyrosine kinases-driven colon cancer cell invasion is induced by Csk membrane delocalization

“…In this context, several candidates have been suggested to disrupt the SH2-pTyr529 intramolecular interaction. These include growth factor receptors, through their association with SFK-SH2 (Mao et al, 1997), and tyrosine phosphatases that dephosphorylate pTyr529 (Liang et al, 2007;Zhu et al, 2007;Zheng et al, 2008). Although probably activated in a subset of tumours, they may not account for the kinase deregulation observed in CRC.…”