Multiple roles of PTEN isoforms PTENα and PTENβ in cellular activities and tumor development

PTEN is a powerful tumor suppressor gene frequently mutated in human cancers and autism spectrum disorders.PTEN protein is located both in the cytoplasm and nucleus and can also be secreted from cells.The best characterized function of PTEN is its ability to dephosphorylate Ptdlns(3,4,5)P3 and converts it back into PIP2 in the cytoplasm,therefore antagonizing the PI3K/AKT pathway which is mainly involved in regulation of cell growth,differentiation,proliferation and invasion(Hopkins et al.,2014;Lee et al.,2018).It has been demonstrated that the nuclear PTEN mainly participates in the maintenance of chromosome stability and regulation of DNA repair pathway(Shen et al.,2007).More recently,nuclear PTEN is also shown to interact with the splicing machinery,spliceosome,to regulate its assembly and pre-mRNA splicing(Shen et al.,2018).In human genome,there is only one gene that encodes PTEN.However,more and more lines of evidence indicate that the PTEN gene may translate isoforms that function differently from canonical PTEN protein.