Mitogen activated protein kinase phosphatases and cancer

Abstract

Deregulation of cell signaling is a vital part of cancer development. The mitogen activated protein kinase (MAPK) family is involved in regulating both cell growth and cell death. This family of kinases is negatively regulated by mitogen activated protein kinase phosphatases (MKPs). MKPs are dual specificity phosphatases that target threonine and tyrosine residues that appear in a TXY motif. There are eleven members of the MKP family. Expression of MKPs has been shown to be altered in many different types of cancer. Most of what is known centers on MKP-1, MKP-2 and MKP-3. This review will focus on their role in cancer development and progression.

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

“…Next, we studied the effects of PROX1 on the stimulation of multiple intracellular signaling pathways involved in apoptosis, proliferation, angiogenesis, lymphangiogenesis, and EMT of gastric cancer cells to determine the mechanisms underlying the effects of PROX1. Wnt/b-catenin/Tcell factor (TCF) and MAPK signaling pathways are involved in the migration, adhesion, proliferation, survival, EMT, angiogenesis, and lymphangiogenesis of various human cancer cells [32,33]. We observed that phosphorylation of b-catenin was increased and that of ERK1/2, p38, and JNK was decreased after PROX1 knockdown.…”

Department of ENT, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China

“…This data suggested that, as a whole, the function of MKP-5 on the three MAPK pathways is similar to that of MKP-1 (JNK = p38 > ERK), which is regarded as a tumor regulator according to the cancer type (5,6). To obtain further insight on the role of MKP-5 in tumor formation, we examined the expression levels of the MKP-5 gene in colon carcinoma (Fig.…”

“…The roles of MKPs in the regulation of MAPK pathways in normal cells suggest that the possible pathological consequences of either a loss or gain in the function of these enzymes are part of the oncogenic process (4)(5)(6)(7). In addition, MAPK signaling plays a key role in determining the response of tumor cells to conventional cancer therapies (7).…”

“…In addition, MAPK signaling plays a key role in determining the response of tumor cells to conventional cancer therapies (7). There is increasing evidence that some MKPs may be abnormally regulated in certain tumors (4)(5)(6). Whether overexpression or loss of expression is a cause of, or contributes to the malignant phenotype rather than simply being a consequence of cell transformation remains ambiguous.…”

“…To clarify whether or not MKP-5 is a genuine regulator of the JNK and p38 pathways, we analyzed the interactions (4)(5)(6). In contrast, involvement of subgroup III MKPs in tumor formation and progression has not been thoroughly examined.…”