PRL PTPs: mediators and markers of cancer progression

Abstract

Aberrant protein tyrosine phosphorylation resulting from the altered activity of protein tyrosine phosphatases (PTPs) is increasingly being implicated in the genesis and progression of human cancer. Accumulating evidence indicates that the dysregulated expression of members of the phosphatase of regenerating liver (PRL) subgroup of PTPs is linked to these processes. Enhanced expression of the PRLs, notably PRL-1 and PRL-3, promotes the acquisition of cellular properties that confer tumorigenic and metastatic abilities. Up-regulation of PRL-3 is associated with the progression and eventual metastasis of several types of human cancer. Indeed, PRL-3 shows promise as a biomarker and prognostic indicator in colorectal, breast, and gastric cancers. However, the substrates and molecular mechanisms of action of the PRLs have remained elusive. Recent findings indicate that PRLs may function in regulating cell adhesion structures to effect epithelial-mesenchymal transition. The identification of PRL substrates is key to understanding their roles in cancer progression and exploiting their potential as exciting new therapeutic targets for cancer treatment.

Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer

“…PRLs are highly expressed in various cancers, especially in metastatic cancers (2). Thus, PRL family has been implicated as a candidate for a biomarker in metastatic and advanced cancers.…”

“…However, PRL-3 is primarily expressed in heart and skeletal muscle, although low level expression can be detected in other tissues as well (2,19). So it has been thought that they function in basic processes common to many tissues and cell types (20).…”

“…So it has been thought that they function in basic processes common to many tissues and cell types (20). Many tissues that do not express or express only low levels of PRL-3 except heart and skeletal muscle are unable to cope with elevated levels of its activity and thus are susceptible to the tumorigenic effects of PRL-3 (2). For this reason, many studies have focused on PRL-3 in lung cancer.…”

“…One such phosphatase, protein tyrosine phosphatase (PTP), catalyzes the hydrolysis of phosphate monoesters specifically on tyrosine residues (1) and members of the PTP family regulate a variety of cellular processes, especially post-translational modification by participating in every aspect of cellular physiologic and pathogenic process (1,2).…”

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).…”