Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma
PIN1 is a peptidyl-prolyl cis/trans isomerase that specifically binds and catalyzes the cis/trans isomerization of the phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif of its interacting proteins. Through this phosphorylation-dependent prolyl isomerization, PIN1 is...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00369/full |
| _version_ | 1819153850178732032 |
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| author | Chi-Wai Cheng Eric Tse |
| author_facet | Chi-Wai Cheng Eric Tse |
| author_sort | Chi-Wai Cheng |
| collection | DOAJ |
| description | PIN1 is a peptidyl-prolyl cis/trans isomerase that specifically binds and catalyzes the cis/trans isomerization of the phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif of its interacting proteins. Through this phosphorylation-dependent prolyl isomerization, PIN1 is involved in the regulation of various important cellular processes including cell cycle progression, cell proliferation, apoptosis and microRNAs biogenesis; hence its dysregulation contributes to malignant transformation. PIN1 is highly expressed in hepatocellular carcinoma (HCC). By fine-tuning the functions of its interacting proteins such as cyclin D1, x-protein of hepatitis B virus and exportin 5, PIN1 plays an important role in hepatocarcinogenesis. Growing evidence supports that targeting PIN1 is a potential therapeutic approach for HCC by inhibiting cell proliferation, inducing cellular apoptosis, and restoring microRNAs biogenesis. Novel formulation of PIN1 inhibitors that increases in vivo bioavailability of PIN1 inhibitors represents a promising future direction for the therapeutic strategy of HCC treatment. In this review, the mechanisms underlying PIN1 over-expression in HCC are explored. Furthermore, we also discuss the roles of PIN1 in HCC tumorigenesis and metastasis through its interaction with various phosphoproteins. Finally, recent progress in the therapeutic options targeting PIN1 for HCC treatment is examined and summarized. |
| first_indexed | 2024-12-22T15:11:44Z |
| format | Article |
| id | doaj.art-3f4b5820d613422889211c9511f2709e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-22T15:11:44Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-3f4b5820d613422889211c9511f2709e2022-12-21T18:21:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-01-01710.3389/fcell.2019.00369501527Targeting PIN1 as a Therapeutic Approach for Hepatocellular CarcinomaChi-Wai ChengEric TsePIN1 is a peptidyl-prolyl cis/trans isomerase that specifically binds and catalyzes the cis/trans isomerization of the phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif of its interacting proteins. Through this phosphorylation-dependent prolyl isomerization, PIN1 is involved in the regulation of various important cellular processes including cell cycle progression, cell proliferation, apoptosis and microRNAs biogenesis; hence its dysregulation contributes to malignant transformation. PIN1 is highly expressed in hepatocellular carcinoma (HCC). By fine-tuning the functions of its interacting proteins such as cyclin D1, x-protein of hepatitis B virus and exportin 5, PIN1 plays an important role in hepatocarcinogenesis. Growing evidence supports that targeting PIN1 is a potential therapeutic approach for HCC by inhibiting cell proliferation, inducing cellular apoptosis, and restoring microRNAs biogenesis. Novel formulation of PIN1 inhibitors that increases in vivo bioavailability of PIN1 inhibitors represents a promising future direction for the therapeutic strategy of HCC treatment. In this review, the mechanisms underlying PIN1 over-expression in HCC are explored. Furthermore, we also discuss the roles of PIN1 in HCC tumorigenesis and metastasis through its interaction with various phosphoproteins. Finally, recent progress in the therapeutic options targeting PIN1 for HCC treatment is examined and summarized.https://www.frontiersin.org/article/10.3389/fcell.2019.00369/fullPIN1phosphorylationhepatocellular carcinomainhibitorhepatocarcinogenesis |
| spellingShingle | Chi-Wai Cheng Eric Tse Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma Frontiers in Cell and Developmental Biology PIN1 phosphorylation hepatocellular carcinoma inhibitor hepatocarcinogenesis |
| title | Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma |
| title_full | Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma |
| title_fullStr | Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma |
| title_full_unstemmed | Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma |
| title_short | Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma |
| title_sort | targeting pin1 as a therapeutic approach for hepatocellular carcinoma |
| topic | PIN1 phosphorylation hepatocellular carcinoma inhibitor hepatocarcinogenesis |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00369/full |
| work_keys_str_mv | AT chiwaicheng targetingpin1asatherapeuticapproachforhepatocellularcarcinoma AT erictse targetingpin1asatherapeuticapproachforhepatocellularcarcinoma |