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Updated: Feb 7, 2026

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Angiopoietin-like protein 3 blocks nuclear import of FAK and contributes to sorafenib response

Yi Bao1, Fu Yang2, Bing Liu1

  • 1Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.

British Journal of Cancer
|July 24, 2018
PubMed
Abstract

Insights

Angiopoietin-like protein 3 (ANGPTL3) predicts sorafenib response in renal cell carcinoma (RCC). Upregulating ANGPTL3 enhances sorafenib sensitivity by inhibiting FAK, improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sorafenib resistance is a significant clinical challenge for renal cell carcinoma (RCC) patients.
  • Understanding mechanisms of sorafenib resistance is crucial for improving therapeutic outcomes.

Purpose of the Study:

  • To investigate the role of Angiopoietin-like protein 3 (ANGPTL3) in sorafenib response in RCC.
  • To elucidate the underlying molecular mechanisms by which ANGPTL3 influences sorafenib efficacy.

Main Methods:

  • ANGPTL3 protein levels were assessed in RCC patient cohorts using western blot and immunohistochemistry.
  • Loss-of-function and gain-of-function experiments were conducted in RCC cells to evaluate ANGPTL3's biological roles.
  • Proteomic and immunoprecipitation analyses were employed to explore ANGPTL3's molecular interactions.

Main Results:

  • ANGPTL3 was found to be upregulated in sorafenib-responsive RCC, correlating with positive clinical responses.
  • Knockdown of ANGPTL3 induced sorafenib tolerance, while its overexpression restored sensitivity.
  • Mechanistically, ANGPTL3 binds to Focal Adhesion Kinase (FAK), preventing sorafenib-induced FAK nuclear translocation, thereby attenuating p53 ubiquitination and promoting apoptosis.

Conclusions:

  • ANGPTL3 serves as a potential predictive biomarker for sorafenib therapy response in RCC.
  • ANGPTL3 represents a promising therapeutic target for overcoming sorafenib resistance and enhancing treatment efficacy.

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