Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

Abstract

Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threonine-tyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signal-regulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment.

Keywords: Carcinogenesis; DUSP1/MKP1; JNK; tumor therapy.

Figure 1

(A) Chemo‐drugs and radiation increased DUSP1 in tumor cells and decreased JNK‐induced apoptosis. (B) CD206 and TGF‐beta promoted HCC progression. Sorafenib inhibited HCC progression via decreasing DUSP1 in M2 macrophages and therefore decreased CD206 and TGF‐beta release. (C) Trastuzumad inhibited HER2 positive breast tumor cells via binding to HER2 to inhibit DUSP1 and therefore induced apoptosis in tumor cells. Trastuzumad‐resistant cells obtained a higher DUSP1 expression and abolished the drug effect.