The small molecule genkwanine M induces single mode, mesenchymal tumor cell motility.

Abstract:

:Individual tumor cells utilize one of two modes of motility to invade the extracellular matrix, mesenchymal or amoeboid. We have determined that the diterpenoid genkwanine M (GENK) enhances the mesenchymal mode of cell motility that is intrinsic to HT-1080 osteosarcoma cells, stimulates a mesenchymal mode of motility in stationary MDA-MB-453 breast carcinoma cells, and induces a shift to a mesenchymal mode of cell motility in LS174T colorectal adenocarcinoma cells that normally utilize the alternate amoeboid mode of motility. The ability of GENK to stimulate or induce mesenchymal motility was preceded by a rapid cell spreading, elongation and polarization that did not require new gene expression. However, these initial morphologic changes were integrin dependent and they were associated with a reorganization of focal contacts and focal adhesions as well as an activation of the focal adhesion kinase. Therefore, GENK induces a mesenchymal mode of cell motility in a wide variety of tumor cell types that may be mediated, at least in part, by an activation of integrin-associated signaling.

journal_name

Exp Cell Res

authors

Zimmerman C,Austin P,Khong A,McLeod S,Bean B,Forestieri R,Andersen RJ,Jan E,Roberge M,Roskelley CD

doi

10.1016/j.yexcr.2013.01.005

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

908-17

issue

6

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(13)00008-6

journal_volume

319

pub_type

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