title: Understanding the role of PIN1 in hepatocellular carcinoma.
abstract: PIN1 is a peptidyl-prolylcis/transisomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation. PIN1 has been found to be over-expressed in many cancers, including human hepatocellular carcinoma (HCC). It has been shown previously that overexpression of PIN1 contributes to the development of HCCin-vitroand in xenograft mouse model. In this review, we first discussed the aberrant transcription factor expression, miRNAs dysregulation,PIN1gene promoter polymorphisms and phosphorylation of PIN1 as potential mechanisms underlying PIN1 overexpression in cancers. Furthermore, we also examined the role of PIN1 in HCC tumourigenesis by reviewing the interactions between PIN1 and various cellular and viral proteins that are involved in β-catenin, NOTCH, and PI3K/Akt/mTOR pathways, apoptosis, angiogenesis and epithelial-mesenchymal transition. Finally, the potential of PIN1 inhibitors as an anti-cancer therapy was explored and discussed.
authors.affiliation: Chi-Wai Cheng, Ka-Wai Leong, Eric Tse, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Chi-Wai Cheng, Ka-Wai Leong, Eric Tse, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Leong
authors.affiliation: Chi-Wai Cheng, Ka-Wai Leong, Eric Tse, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Eric
authors.initials: E
authors.lastname: Tse
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt; D051880:Receptors, Notch; D015398:Signal Transduction; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D051176:beta Catenin
chemical_list: D019938:Cyclin D1; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051880:Receptors, Notch; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D051176:beta Catenin; C107489:BIRC5 protein, human
keywords: Hepatocarcinogenesis; Hepatocellular carcinoma; Isomerization; PIN1; Phosphorylation