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


RESULTS
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.


CONCLUSIONS
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.
Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, London, United Kingdom.
Ilan
I
Elson-Schwab
Anna
A
Lorentzen
Christopher J
CJ
Marshall
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008545:Melanoma / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009361:Neoplasm Invasiveness
D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate