MicroRNA-200 Family Members Differentially Regulate Morphological Plasticity and Mode of Melanoma Cell Invasion

PLoS One

Ilan Elson-Schwab¹  Anna Lorentzen¹  Christopher J. Marshall¹ 

[1] Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, London, United Kingdom

关键词: Melanoma cells;    MicroRNAs;    Melanomas;    Collagens;    Melanocytes;    Transfection;    Small interfering RNAs;    Cancer cell migration;   

DOI  :  10.1371/journal.pone.0013176

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY