Fad104, a positive regulator of adipocyte differentiation, suppresses invasion and metastasis of melanoma cells by inhibition of STAT3 activity

PLoS One. 2015 Feb 11;10(2):e0117197. doi: 10.1371/journal.pone.0117197. eCollection 2015.

Abstract

Metastasis is the main cause of death in patients with cancer, and understanding the mechanisms of metastatic processes is essential for the development of cancer therapy. Although the role of several cell adhesion, migration or proliferation molecules in metastasis is established, a novel target for cancer therapy remains to be discovered. Previously, we reported that fad104 (factor for adipocyte differentiation 104), a regulatory factor of adipogenesis, regulates cell adhesion and migration. In this report, we clarify the role of fad104 in the invasion and metastasis of cancer cells. The expression level of fad104 in highly metastatic melanoma A375SM cells was lower than that in poorly metastatic melanoma A375C6 cells. Reduction of fad104 expression enhanced the migration and invasion of melanoma cells, while over-expression of FAD104 inhibited migration and invasion. In addition, melanoma cells stably expressing FAD104 showed a reduction in formation of lung colonization compared with control cells. FAD104 interacted with STAT3 and down-regulated the phosphorylation level of STAT3 in melanoma cells. These findings together demonstrate that fad104 suppressed the invasion and metastasis of melanoma cells by inhibiting activation of the STAT3 signaling pathway. These findings will aid a comprehensive description of the mechanism that controls the invasion and metastasis of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / pathology*
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Movement
  • Fibronectins / genetics
  • Fibronectins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • FNDC3B protein, human
  • Fibronectins
  • STAT3 Transcription Factor

Grants and funding

This work was supported in part by grants from the Japan Society for the Promotion of Science (JSPS): (http://www.jsps.go.jp/), 21390024 (MI), Aichi Cancer Research Foundation: (http://www.acrf.or.jp/) (MN), and The Research Foundation for Pharmaceutical Sciences, Japan: (http://www15.ocn.ne.jp/~yakusho/) (MN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.