Differential Depth Sensing Reduces Cancer Cell Proliferation via Rho-Rac-Regulated Invadopodia

Bone, which is composed of a porous matrix, is one of the principal secondary locations for cancer. However, little is known about the effect of this porous microenvironment in regulating cancer cell proliferation. Here, we examine how the depth of the pores can transduce a mechanical signal and red...

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Bibliographic Details
Published in:ACS nano 2017-07, Vol.11 (7), p.7336-7348
Main Authors: Chaudhuri, Parthiv Kant, Pan, Catherine Qiurong, Low, Boon Chuan, Lim, Chwee Teck
Format: Article
Language:English
Subjects:
Actomyosin - metabolism
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line
Cell Line, Tumor
Cell Proliferation
Female
Humans
MAP Kinase Signaling System
MCF-7 Cells
Mechanotransduction, Cellular
Podosomes - metabolism
Podosomes - pathology
Porosity
rac GTP-Binding Proteins - metabolism
rho-Associated Kinases - metabolism
Signal Transduction
Tumor Microenvironment
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Summary:Bone, which is composed of a porous matrix, is one of the principal secondary locations for cancer. However, little is known about the effect of this porous microenvironment in regulating cancer cell proliferation. Here, we examine how the depth of the pores can transduce a mechanical signal and reduce the proliferation of noncancer breast epithelial cells (MCF-10A) and malignant breast cancer cells (MDA-MB-231 and MCF-7) using micrometer-scale topographic features. Interestingly, cells extend actin-rich protrusions, such as invadopodia, to sense the depth of the matrix pore and activate actomyosin contractility to decrease MCF-10A proliferation. However, in MDA-MB-231, depth sensing inactivates Rho-Rac-regulated actomyosin contractility and phospho-ERK signaling. Inhibiting contractility on this porous matrix using blebbistatin further reduces MDA-MB-231 proliferation. Our findings support the notion of mechanically induced dormancy through depth sensing, where invadopodia-mediated depth sensing can inhibit the proliferation of noncancer and malignant breast cancer cells through differential regulation of actomyosin contractility.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.7b03452