Critical role of XBP1 in cancer signalling is regulated by PIN1

Chae, Unbin; Park, Sun-Ji; Wei, Shou; Min, Ju-Sik; Lee, Jun-Hyeog; Park, Se Hoon; Lee, Ann–Hwee; Lu, Kun Ping; Lee, Dong‐Seok; Min, Sang‐Hyun

doi:10.1042/bcj20160482

Cited by 13 publications

(20 citation statements)

References 30 publications

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“…Pin1 also stabilizes bromodomain-containing protein 4 (BRD4), a transactivator of multiple oncogenes, to promote the proliferation, migration, and invasion of gastric cancer 62 . Besides, Pin1 upregulates many other proliferation-inducing factors, including β-catenin 63 , FoxM1 64 , XBP1 65 , NUR77 66 , c-Jun 67 , and c-Myc 68 .…”

Section: Introductionmentioning

confidence: 99%

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

et al. 2018

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Pin1 is the only known peptidyl-prolyl cis–trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.

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Section: Introductionmentioning

confidence: 99%

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

et al. 2018

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“…However, there is no single mechanism that can fully explain the pathogenesis of tumor cell hyper-proliferation in HCC. Recent studies revealed that XBP1 was closely linked with tumor occurrence ( 4 , 8 , 10 – 12 ). Numerous researches have reported that the IRE1/XBP1 pathway is involved in cell survival, epithelial-mesenchymal transition, transcription factor regulation, drug resistance and glycolysis in tumor cells ( 8 – 13 ).…”

Section: Discussionmentioning

confidence: 99%

Low expression of miR‑199 in hepatocellular carcinoma contributes to tumor cell hyper‑proliferation by negatively suppressing XBP1

et al. 2018

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide, and microRNAs (miRs) are considered to serve important functions in the pathogenesis of HCC by regulating the expression of specific target genes. The present study was conducted to investigate the role of miR-199 and its putative target X-box binding protein 1 (XBP1) in HCC, as well as of the downstream gene cyclin D. The expression levels of miR-199, XBP1 and cyclin D were detected in clinical HCC specimens. The effect of miR-199 on the regulation of HCC cell proliferation and its underlying mechanism were examined in Hep3B2.1–7 cells, through expression assays and measurement of cell proliferation (via Cell Counting Kit-8, and 5-ethynyl-2′-deoxyuridine and DAPI double-staining assays) coupled with gain- and lose- of function experiments. The expression of XBP1 and cyclin D was significantly increased in HCC tissues when compared with adjacent non-HCC tissues, while the expression of miR-199 was decreased. Exogenous miR-199 significantly suppressed the expression of XBP1 and cyclin D in Hep3B2.1–7 cells. However, the expression of XBP1 and cyclin D significantly increased on treatment with miR-199 inhibitor. Consistently, Hep3B2.1–7 cells co-transfected with a wild type reporter plasmid [XBP1-3′untranslated region (UTR)-WT] and exogenous miR-199 exhibited lower relative luciferase enzyme activity than cells co-transfected with negative control miRNA and XBP1-3′UTR-WT, while cells co-transfected with mutated plasmid (XBP1-3′UTR-MU) and miR-199 exhibited no change. It was further observed that knockdown of XBP1 by small interfering RNA significantly decreased the expression of cyclin D in Hep3B2.1–7 cells. Additionally, exogenous miR-199 decreased the proliferation of Hep3B2.1–7 cells, which was contrary to the effect of miR-199 inhibitor. In conclusion, it was demonstrated that miR-199 negatively regulated the expression of XBP1 by directly binding to its 3′UTR and that XBP1 impacted cyclin D expression, which was associated with the cell cycle regulation in Hep3B2.1–7 cells. These findings suggested that a miR-199/XBP1/cyclin D axis may serve an important role in the pathogenesis of HCC.

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“…On the contrary, p53 and AP4 act as transcriptional repressors and reduce the Pin1 transcription (Mitchell and Smith, 1988;Jeong et al, 2014). Xbp1 induces the transcription of p53 via HEPN1 and represses E2F1 via NF-κB activation, resulting in reduced Pin1 transcription (Chae et al, 2016). The transcription of PIN1 is repressed by BRCA1, a tumor suppressor gene (MacLachlan et al, 2000).…”

Section: Transcriptional and Post-translational Regulation Of Pin1 Inmentioning

confidence: 99%

“…PIN1 stabilizes BRD4 protein to increase the migration and proliferation of gastric cancer (Hu et al, 2017). It also upregulates c-Jun, c-Myc, FoxM1, β-catenin, NUR77, and XBP1 (Chen et al, 2012;Helander et al, 2015;Chae et al, 2016;Kruiswijk et al, 2016;Zhu et al, 2016;Csizmok et al, 2018).…”

Section: Transcriptional and Post-translational Regulation Of Pin1 Inmentioning

confidence: 99%

Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics

Min

2020

Front. Cell Dev. Biol.

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Peptidyl-prolyl isomerase (PIN1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which results in the alteration of protein structure, function, and stability. The altered structure and function of these phosphorylated proteins regulated by PIN1 are closely related to cancer development. PIN1 is highly expressed in human cancers and promotes cancer as well as cancer stem cells by breaking the balance of oncogenes and tumor suppressors. In this review, we discuss the roles of PIN1 in cancer and PIN1-targeted small-molecule compounds.

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Critical role of XBP1 in cancer signalling is regulated by PIN1

Cited by 13 publications

References 30 publications

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy

Low expression of miR‑199 in hepatocellular carcinoma contributes to tumor cell hyper‑proliferation by negatively suppressing XBP1

Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics

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