title: The PTEN tumor suppressor gene and its role in lymphoma pathogenesis.
abstract: The phosphatase and tensin homolog gene PTEN is one of the most frequently mutated tumor suppressor genes in human cancer. Loss of PTEN function occurs in a variety of human cancers via its mutation, deletion, transcriptional silencing, or protein instability. PTEN deficiency in cancer has been associated with advanced disease, chemotherapy resistance, and poor survival. Impaired PTEN function, which antagonizes phosphoinositide 3-kinase (PI3K) signaling, causes the accumulation of phosphatidylinositol (3,4,5)-triphosphate and thereby the suppression of downstream components of the PI3K pathway, including the protein kinase B and mammalian target of rapamycin kinases. In addition to having lipid phosphorylation activity, PTEN has critical roles in the regulation of genomic instability, DNA repair, stem cell self-renewal, cellular senescence, and cell migration. Although PTEN deficiency in solid tumors has been studied extensively, rare studies have investigated PTEN alteration in lymphoid malignancies. However, genomic or epigenomic aberrations of PTEN and dysregulated signaling are likely critical in lymphoma pathogenesis and progression. This review provides updated summary on the role of PTEN deficiency in human cancers, specifically in lymphoid malignancies; the molecular mechanisms of PTEN regulation; and the distinct functions of nuclear PTEN. Therapeutic strategies for rescuing PTEN deficiency in human cancers are proposed.
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230, USA.|Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230, USA.|The University of Texas Graduate School of Biomedical Science, Houston, TX 77230, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase
keywords: AKT; PI3K; PTEN; diffuse large B-cell lymphoma; lymphoid malignancies; mTOR; tumor suppressor