Correction for Targeted inactivation of β1 integrin induces β3 integrin switching, which drives breast cancer metastasis by TGF-β

2014 ◽  
Vol 25 (4) ◽  
pp. 548-548
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Β1 Integrin ◽  
Β3 Integrin ◽  
Targeted Inactivation

scholarly journals Targeted inactivation of β1 integrin induces β3 integrin switching, which drives breast cancer metastasis by TGF-β

2013 ◽  
Vol 24 (21) ◽  
pp. 3449-3459 ◽  
Author(s):  
Jenny G. Parvani ◽  
Amy J. Galliher-Beckley ◽  
Barbara J. Schiemann ◽  
William P. Schiemann
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Β1 Integrin ◽  
Metastatic Progression ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Β3 Integrin

Mammary tumorigenesis and epithelial–mesenchymal transition (EMT) programs cooperate in converting transforming growth factor-β (TGF-β) from a suppressor to a promoter of breast cancer metastasis. Although previous reports associated β1 and β3 integrins with TGF-β stimulation of EMT and metastasis, the functional interplay and plasticity exhibited by these adhesion molecules in shaping the oncogenic activities of TGF-β remain unknown. We demonstrate that inactivation of β1 integrin impairs TGF-β from stimulating the motility of normal and malignant mammary epithelial cells (MECs) and elicits robust compensatory expression of β3 integrin solely in malignant MECs, but not in their normal counterparts. Compensatory β3 integrin expression also 1) enhances the growth of malignant MECs in rigid and compliant three-dimensional organotypic cultures and 2) restores the induction of the EMT phenotypes by TGF-β. Of importance, compensatory expression of β3 integrin rescues the growth and pulmonary metastasis of β1 integrin–deficient 4T1 tumors in mice, a process that is prevented by genetic depletion or functional inactivation of β3 integrin. Collectively our findings demonstrate that inactivation of β1 integrin elicits metastatic progression via a β3 integrin–specific mechanism, indicating that dual β1 and β3 integrin targeting is necessary to alleviate metastatic disease in breast cancer patients.

scholarly journals NR4A1 Antagonists Inhibit β1-Integrin-Dependent Breast Cancer Cell Migration

2016 ◽  
Vol 36 (9) ◽  
pp. 1383-1394 ◽  
Author(s):  
Erik Hedrick ◽  
Syng-Ook Lee ◽  
Ravi Doddapaneni ◽  
Mandip Singh ◽  
Stephen Safe
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Nuclear Export ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Breast Cancer Metastasis ◽  
Β1 Integrin ◽  
Breast Cancer Patients ◽  
Β3 Integrin

Overexpression of the nuclear receptor 4A1 (NR4A1) in breast cancer patients is a prognostic factor for decreased survival and increased metastasis, and this has been linked to NR4A1-dependent regulation of transforming growth factor β (TGF-β) signaling. Results of RNA interference studies demonstrate that basal migration of aggressive SKBR3 and MDA-MB-231 breast cancer cells is TGF-β independent and dependent on regulation of β1-integrin gene expression by NR4A1 which can be inhibited by the NR4A1 antagonists 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) and a relatedp-carboxymethylphenyl [1,1-bis(3′-indolyl)-1-(p-carboxymethylphenyl)methane (DIM-C-pPhCO2Me)] analog. The NR4A1 antagonists also inhibited TGF-β-induced migration of MDA-MB-231 cells by blocking nuclear export of NR4A1, which is an essential step in TGF-β-induced cell migration. We also observed that NR4A1 regulates expression of both β1- and β3-integrins, and unlike other β1-integrin inhibitors which induce prometastatic β3-integrin, NR4A1 antagonists inhibit expression of both β1- and β3-integrin, demonstrating a novel mechanism-based approach for targeting integrins and integrin-dependent breast cancer metastasis.

scholarly journals FER kinase promotes breast cancer metastasis by regulating α6- and β1-integrin-dependent cell adhesion and anoikis resistance

Oncogene ◽  
2013 ◽  
Vol 32 (50) ◽  
pp. 5582-5592 ◽  
Author(s):  
I A Ivanova ◽  
J F Vermeulen ◽  
C Ercan ◽  
J M Houthuijzen ◽  
F A Saig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Β1 Integrin ◽  
Anoikis Resistance ◽  
Dependent Cell
Sign in / Sign up

Export Citation Format

Share Document