{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:37:04Z","timestamp":1787884624319,"version":"build-2784847793"},"reference-count":210,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lo Kwee-Seong Biomedical Research Seed Fund","award":["6903806"],"award-info":[{"award-number":["6903806"]}]},{"name":"Pilot Project Fund, The Brain and Mind Institute of the Chinese University of Hong Kong;","award":["4930742 and 4930783"],"award-info":[{"award-number":["4930742 and 4930783"]}]},{"name":"Collaborative Research Fund grants, The Hong Kong University Grants Committee.","award":["C4014-14G"],"award-info":[{"award-number":["C4014-14G"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene frequently found to be inactivated in over 30% of human cancers. PTEN encodes a 54-kDa lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase pathway involved in the promotion of multiple pro-tumorigenic phenotypes. Although the PTEN protein plays a pivotal role in carcinogenesis, cumulative evidence has implicated it as a key signaling molecule in several other diseases as well, such as diabetes, Alzheimer\u2019s disease, and autism spectrum disorders. This finding suggests that diverse cell types, especially differentiated cells, express PTEN. At the cellular level, PTEN is widely distributed in all subcellular compartments and organelles. Surprisingly, the cytoplasmic compartment, not the plasma membrane, is the predominant subcellular location of PTEN. More recently, the finding of a secreted \u2018long\u2019 isoform of PTEN and the presence of PTEN in the cell nucleus further revealed unexpected biological functions of this multifaceted molecule. At the regulatory level, PTEN activity, stability, and subcellular distribution are modulated by a fascinating array of post-translational modification events, including phosphorylation, ubiquitination, and sumoylation. Dysregulation of these regulatory mechanisms has been observed in various human diseases. In this review, we provide an up-to-date overview of the knowledge gained in the last decade on how different functional domains of PTEN regulate its biological functions, with special emphasis on its subcellular distribution. This review also highlights the findings of published studies that have reported how mutational alterations in specific PTEN domains can lead to pathogenesis in humans.<\/jats:p>","DOI":"10.3390\/cancers11091247","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T10:54:53Z","timestamp":1566816893000},"page":"1247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Multifaceted Regulation of PTEN Subcellular Distributions and Biological Functions"],"prefix":"10.3390","volume":"11","author":[{"given":"Tian","family":"Liu","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Room 705, Lo Kwee-Seong Integrated Biomedical Sciences Building, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Room 705, Lo Kwee-Seong Integrated Biomedical Sciences Building, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-0449","authenticated-orcid":false,"given":"Yubing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology, Weifang Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Room 705, Lo Kwee-Seong Integrated Biomedical Sciences Building, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"ref_1","first-page":"2124","article-title":"TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta","volume":"57","author":"Li","year":"1997","journal-title":"Cancer Res."},{"key":"ref_2","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_3","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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