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Updated: Jul 2, 2025

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
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Published on: October 16, 2017

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PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2

Yuming Wang1,2, Yiwei Liu1,2, Hairong Chen3

  • 1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 300 Guangzhou Road, Nanjing, China.

Cellular Oncology (Dordrecht, Netherlands)
|February 22, 2024
PubMed
Abstract

Insights

Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) drives cholangiocarcinoma (CCA) growth and metastasis by regulating ANXA2 phosphorylation. Targeting PIN1 with all-trans retinoic acid (ATRA) shows therapeutic potential for CCA.

Area of Science:

  • Hepatobiliary Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Cholangiocarcinoma (CCA) presents a significant clinical challenge due to poor prognosis and limited treatment options.
  • The role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) in CCA pathogenesis is largely unexplored.
  • Identifying novel therapeutic targets is crucial for improving outcomes in CCA patients.

Purpose of the Study:

  • To investigate the expression and function of PIN1 in cholangiocarcinoma.
  • To elucidate the molecular mechanisms by which PIN1 influences CCA progression.
  • To evaluate the therapeutic potential of targeting PIN1 in CCA.

Main Methods:

  • Assessed PIN1 expression using tissue microarrays and TCGA data.
  • Conducted in vitro and in vivo experiments to evaluate PIN1's role in CCA cell adhesion and metastasis.
  • Utilized RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry to explore downstream pathways.

Main Results:

  • PIN1 overexpression correlated with poor prognosis in CCA and promoted cell proliferation and migration.
  • PIN1 acts as an oncogene by regulating ANXA2 phosphorylation, enhancing CCA cell adhesion.
  • The PIN1/RACK1/ANXA2 complex was identified as a key mediator of CCA progression.
  • Pharmacological inhibition of PIN1 with ATRA suppressed CCA metastasis in vivo.

Conclusions:

  • The PIN1/RACK1/ANXA2 complex plays a critical role in CCA growth and metastasis.
  • Targeting PIN1 represents a promising therapeutic strategy for cholangiocarcinoma.
  • All-trans retinoic acid (ATRA) demonstrates potential as a PIN1 inhibitor for CCA treatment.
Keywords:
ATRAAdhesionCholangiocarcinomaMetastasisPIN1

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