title: Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies.
abstract: Being a tumor suppressor, PTEN functions as a dual-specificity protein and phospholipid phosphatase and regulates a variety of cellular processes and signal transduction pathways. Loss of PTEN function has been detected frequently in different forms of cancers, such as breast, prostate and lung cancer, gastric and colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we provide a summary of PTEN and its role in bone malignancies including bone metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non-genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation. We also discuss the emerging therapeutic applications targeting PTEN loss for the treatment of these bone malignant diseases.
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Qingdao University, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Division in Signaling Biology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D019175:DNA Methylation; D018450:Disease Progression; D014644:Genetic Variation; D006801:Humans; D019656:Loss of Heterozygosity; D035683:MicroRNAs / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C494929:PTEN protein, human
keywords: Akt; BONE METASTASIS; PI3K; PTEN; SARCOMA