Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells

Pin Cyuan Chen, Wen Ying Lee, Hsiang Hsi Ling, Chia Hsiung Cheng, Ku Chung Chen, Cheng Wei Lin

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts. Interestingly, conditioned medium from nicotine-activated fibroblasts (Nic-CM) had a greater impact on promoting the EMT and migratory capability toward cancer cells than did treatment with nicotine alone. Production of connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β by nicotine-treated fibroblasts was demonstrated to be crucial for promoting the EMT and cancer cell migration, and blocking of CTGF and TGF-β in Nic-CM-suppressed tumor motility. Moreover, nicotine induced expressions of CTGF, and TGF-β in fibroblasts as identified through α7 nicotinic acetylcholine receptor (nAChR)-dependent activation of the AKT/TAZ signaling mechanism. Together, our data showed for the first time that activation of fibroblasts is largely responsible for accelerating smoking-mediated breast cancer progression.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • Breast cancer
  • EMT
  • Fibroblasts
  • Nicotine
  • Tumor microenvironment

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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