EXPRESSION AND FUNCTION OF DUAL SPECIFICITY PHOSPHATASE 9 IN BREAST CANCER

Abstract

"This study evaluated the roles of Dual-Specificity Phosphatase 9 (DUSP9) and Protein Tyrosine Phosphatase Mitochondrial 1 (PTPMT1) in breast cancer. We hypothesized that DUSP9 is a tumour promoter and PTPMT1 is tumour suppressor.

DUSP9 knockdown inhibited breast cancer cell migration and invasion, and upregulated PTPMT1. Silencing PTPMT1 enhanced cell migration and invasion, decreased cell viability, and increased apoptosis in breast cancer. Double silencing of both DUSP9 & PTPMT1 promoted breast cancer cell migration and invasion similar to the phenotype observed in PTPMT1 knockdown. DUSP9 knockdown increased the phosphorylation of AMPKα. PTPMT1 silencing upregulated a downstream molecule, Protein Phosphatase 1 Regulatory subunit 3B, PPP1R3B and the activated AMPKα eventually resulting in breast cancer aggression. Also, PTPMT1 knockdown activated pro-apoptotic enzymes caspases-3/7 and subsequent cleavage of poly (ADP-ribose) polymerase 1 leading to apoptosis.

This initial study of DUSP9 and PTPMT1 DUSP9 provides the basis to understanding breast cancer cell aggression and apoptosis."