PRL‐3 phosphatase and cancer metastasis

Abstract

The deregulated expression of members of the phosphatase of regenerating liver (PRL) family has been implicated in the metastatic progression of multiple human cancers. Importantly, PRL-1 and PRL-3 both possess the capacity to drive key steps in metastatic progression. Yet, little is known about the regulation and oncogenic mechanisms of this emerging class of dual-specificity phosphatases. This prospect article details the involvement of PRLs in the metastatic cascade, the regulatory mechanisms controlling PRL expression, and recent efforts in the characterization of PRL-modulated pathways and substrates using biochemical and high-throughput approaches. Current advances and future prospects in anti-cancer therapy targeting this family are also discussed.

A role of autophagy in PTP4A3-driven cancer progression

“…32 In cells with stable ATG5 knockdown, PTP4A3 was unable to promote LC3 conversion upon CQ, rapamycin, or combined CQ and rapamycin treatments (Fig. 3C, red boxes in lanes 2, 8, 14 vs. blue boxes in lanes 5,11,17). Taken together, our results show that PTP4A3 promotes autophagic flux in an ATG5-dependent manner.…”

“…11 In light of our data suggesting that PTP4A3 could promote autophagy, which in turn has established associations with tumor biology, 9 we further investigated the role of autophagy in PTP4A3-mediated cancer progression. First, we compared the growth of A2780-Vec and A2780-PTP4A3 cells following depletion of PIK3C3, BECN1, or ATG5 expression.…”

“…10 It is best known for its role in promoting cancer metastasis. 11 Upregulation of PTP4A3 in metastatic specimens from colorectal cancer was reported a decade ago. 12 The oncogenic roles of PTP4A3 overexpression include increased cell migration/invasion in vitro, and enhanced metastasis in vivo through activation of the Rho GTPase family and the phosphoinositide 3-kinase-AKT pathway.…”

Phosphatase of Regenerating Liver 2 (PRL2) Deficiency Impairs Kit Signaling and Spermatogenesis

“…The phosphatase of regenerating liver (PRL) 2 family of proteins are potential targets in oncology (1)(2)(3). Of the three PRLs, PRL2 is the most abundantly and ubiquitously expressed in adult human tissues while PRL1 has a somewhat more restricted pattern of expression and an overall lower level than PRL2 (4 -6).…”

“…PRL3 is primarily expressed in heart and skeletal muscle (5,7). Unlike most protein phosphatases that function to reverse the action of protein kinases, the PRLs play a positive role in promoting cell proliferation and invasion (1)(2)(3). PRLs are found elevated in colorectal (8,9), liver (10), prostate (11), pancreatic (12), and breast (13) cancers, as well as hematological malignancies such as multiple myeloma (14,15) and acute myeloid leukemia (16,17).…”