MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion

PLoS One. 2010 Oct 4;5(10):e13176. doi: 10.1371/journal.pone.0013176.

Abstract

Background: A functional role of microRNAs (miRNAs or miRs) in neoplasia and metastasis is becoming clear, and the miR-200 family has received much attention for potentially regulating tumor progression. The miRNAs of this family have been shown to suppress epithelial-mesenchymal transition, and their down-regulation in some tumors promotes invasion and metastasis. Interestingly, while miR-200 is down-regulated in some cancers, it is up-regulated in others.

Principal findings: We show that levels of miR-200 are increased in melanoma cell lines compared to normal melanocytes and that miR-200 family members play a role in determining modes of tumor cell migration. Individual tumor cells can invade in either elongated, "mesenchymal-type" or rounded, "amoeboid-like" modes and these two modes of invasion are inter-convertible [1]. In melanoma cell lines, expression of miR-200 members does not suppress invasion but rather leads to a switch between modes of invasion. MicroRNA-200c results in a higher proportion of cells adopting the rounded, amoeboid-like mode of invasion, while miR-200a results in a protrusion-associated elongated mode of invasion. Functional target identification studies suggest that the morphological effects of miR-200c may be mediated by reduced expression of MARCKS, which has been linked to formation of cell protrusions. In contrast miR-200a reduces actomyosin contractility, a feature of rounded morphology.

Significance: Overall our findings call into question the general role of miR-200 in suppressing invasion and metastasis, and highlight novel distinguishing characteristics of individual miR-200 family members.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Melanoma / pathology*
  • Membrane Proteins / physiology
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Neoplasm Invasiveness*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MARCKS protein, human
  • Membrane Proteins
  • Myristoylated Alanine-Rich C Kinase Substrate