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PIP3 levels, though, increase quickly and transiently after growth factor addition, upon activation of phosphatidylinositol 3-kinase (PI3-kinase). PIP3 is required for the activation of intracellular signaling pathways that induce cell proliferation, cell migration, and survival. Given the critical role of this second messenger for cellular responses, PIP3 levels must be tightly regulated. The lipid phosphatase PTEN (phosphatase and tensin-homolog in chromosome 10) is the phosphatase responsible for PIP3 dephosphorylation to PIP2. PTEN tumor suppressor is frequently inactivated in endometrium and prostate carcinomas, and also in glioblastoma, illustrating the contribution of elevated PIP3 levels for cancer development. PTEN biological activity can be modulated by heterozygous gene loss, gene mutation, and epigenetic or transcriptional alterations. In addition, PTEN can also be regulated by post-translational modifications. Acetylation, oxidation, phosphorylation, sumoylation, and ubiquitination can alter PTEN stability, cellular localization, or activity, highlighting the complexity of PTEN regulation. While current strategies to treat tumors exhibiting a deregulated PI3-kinase\/PTEN axis have focused on PI3-kinase inhibition, a better understanding of PTEN post-translational modifications could provide new therapeutic strategies to restore PTEN action in PIP3-dependent tumors.<\/jats:p>","DOI":"10.3390\/cancers14225613","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:36:36Z","timestamp":1668566196000},"page":"5613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Targeting PTEN Regulation by Post Translational Modifications"],"prefix":"10.3390","volume":"14","author":[{"given":"Ana","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Cantoblanco, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-3330","authenticated-orcid":false,"given":"Antonio","family":"Garrido","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Cantoblanco, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3999-5434","authenticated-orcid":false,"given":"Ana C.","family":"Carrera","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, Cantoblanco, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1126\/science.275.5308.1943","article-title":"PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer","volume":"275","author":"Li","year":"1997","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ng0497-356","article-title":"Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers","volume":"15","author":"Steck","year":"1997","journal-title":"Nat. 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