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AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Bo Chen1, Jin Wang1, Danian Dai1

  • 1Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 East Dongfeng Road, Guangzhou, 510060, People's Republic of China.

Journal of Experimental & Clinical Cancer Research : CR
|May 13, 2017
PubMed
Abstract

Insights

The AHNAK protein acts as a tumor suppressor in triple-negative breast cancer (TNBC). Its down-regulation correlates with poor prognosis, while its restoration inhibits TNBC cell growth and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • AHNAK (desmoyokin) is a large protein implicated in various cancer functions.
  • Its role in triple-negative breast cancer (TNBC) remains to be fully elucidated.

Purpose of the Study:

  • To investigate the role of AHNAK in triple-negative breast cancer (TNBC).
  • To determine the prognostic significance of AHNAK expression in TNBC patients.

Main Methods:

  • Analysis of AHNAK mRNA levels in breast cancer cell lines and patient tumors.
  • Correlation analysis between AHNAK expression and clinicopathological features in TNBC.
  • In vitro and in vivo functional assays of AHNAK in TNBC cell lines.
  • Investigation of signaling pathways involved in AHNAK's tumor-suppressive effects.

Main Results:

  • AHNAK mRNA was down-regulated in most human breast cancer cell lines, particularly in TNBC.
  • Reduced AHNAK expression correlated significantly with advanced tumor status, lymph node infiltration, and TNM stage in TNBC patients.
  • AHNAK overexpression suppressed TNBC cell proliferation, colony formation, xenograft growth, and lung metastasis.
  • AHNAK knockdown yielded consistent results, confirming its tumor-suppressive role.

Conclusions:

  • AHNAK functions as a tumor suppressor in triple-negative breast cancer.
  • Down-regulation of AHNAK is an independent prognostic factor for poor survival in TNBC patients.
  • AHNAK exerts its tumor-suppressive effects by modulating the AKT/MAPK and Wnt/β-catenin signaling pathways.
Keywords:
AHNAKAKTMAPKTriple-negative breast cancerWnt/β-catenin pathway

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