Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR/Integrin β1/ Src signaling in triple negative breast cancer cells

Zuhal Hamurcu, Nesrin Delibaşı, Seda Geçene, Elif Funda Şener, Hamiyet Dönmez-Altuntaş, Yusuf Özkul, Halit Canatan, Bulent Ozpolat

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Autophagy is a catabolic process for degrading dysfunctional proteins and organelles, and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in breast cancer cells is not well understood. In the present study, we investigated the role of autophagy in highly aggressive and metastatic triple negative breast cancer (TNBC) and non-metastatic breast cancer cells and demonstrated that the knockdown of autophagy-related genes (LC3 and Beclin-1) inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration/invasion and induced apoptosis in MDA-MB-231 and BT-549 TNBC cells. Knockdown of LC3 and Beclin-1 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, uPAR/integrin-β1/Src, and PARP1. In conclusion, our study suggests that LC3 and Beclin-1 are required for cell proliferation, survival, migration and invasion, and may contribute to tumor growth and progression of highly aggressive and metastatic TNBC cells and therapeutic targeting of autophagy genes may be a potential therapeutic strategy for TNBC in breast cancer.

Original languageEnglish (US)
Pages (from-to)415-430
Number of pages16
JournalJournal of Cancer Research and Clinical Oncology
Volume144
Issue number3
DOIs
StatePublished - Mar 1 2018

Keywords

  • Autophagy
  • Beclin-1 siRNA
  • Breast cancer
  • Invasion
  • LC3
  • Metastasis
  • Migration
  • Proliferation
  • TNBC
  • Treatment
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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