NDLI: LIM kinase inhibition reduces breast cancer growth and invasiveness but systemic inhibition does not reduce metastasis in mice

Content Provider	Springer Nature Link
Author	Li, Rong Doherty, Judy Antonipillai, Juliana Chen, Sheng Devlin, Mark Visser, Kathryn Baell, Jonathan Street, Ian Anderson, Robin L. Bernard, Ora
Copyright Year	2012
Abstract	Metastasis is the major cause of morbidity and mortality in cancer patients. An understanding of the genes that regulate metastasis and development of therapies to target these genes is needed urgently. Since members of the LIM kinase (LIMK) family are key regulators of the actin cytoskeleton and are involved in cell motility and invasion, LIMK is considered to be a good therapeutic target for metastatic disease. Here we investigated the consequences of LIMK inhibition on growth and metastasis of human and mouse mammary tumors. LIMK activity was reduced in tumor cells by expression of dominant-negative LIMK1, by RNA interference or with a selective LIMK inhibitor. The extent of phosphorylation of the LIMK substrate, cofilin, of proliferation and invasion in 2D and 3D culture and of tumor growth and metastasis in mice were assessed. Inhibition of LIMK activity efficiently reduced the pro-invasive properties of tumor cells in vitro. Tumors expressing dominant-negative LIMK1 grew more slowly and were less metastatic in mice. However, systemic administration of a LIMK inhibitor did not reduce either primary tumor growth or spontaneous metastasis. Surprisingly, metastasis to the liver was increased after administration of the inhibitor. These data raise a concern about the use of systemic LIMK inhibitors for the treatment of metastatic breast cancer.
Starting Page	483
Ending Page	495
Page Count	13
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	30
Issue Number	4
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-12-13
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	LIM kinase inhibitors Breast cancer Metastasis Actin cytoskeleton Therapy Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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