Focal Adhesion Kinase Induces Matrix Metalloproteinase-2 by Involving α5β1-Mediated Signaling in Breast Cancer Cell, MCF-7.
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Date
2015-01
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Abstract
Introduction: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a pivotal role in cell invasion. Matrix
metalloproteinases (MMPs) are implicated as the key players in cancer cell invasion. Hence, the role of FAK in MMP regulation
is very important in understanding tumor progression. Materials and Methods: Here, we studied the role of FAK, its association
with other signaling kinases and involvement in the α5β1 integrin receptor-mediated regulation of MMP-2 activity and expression
in human breast cancer cell line MCF-7. Results: Immuno blot analysis revealed that FN treatment causes phosphorylation of
FAK and FAK gets localized at the cell attachment focal point of MCF-7 cells. FN treatment did not change the mRNA status of
FAK but enhanced mRNA level of MMP-2 and MT1-MMP, also caused downregulation of TIMP-2. Co-imunoprecipitation and
inhibitor studies revealed the association of FAK with α5β1, Paxillin, PI3K and ERK. siRNA studies revealed that FAK is critical in
regulation of activity and expression of MMP-2 and downstream signaling kinases. Conclusion: Th e interaction of α5β1 integrin
with FN initiates a signaling cascade with FAK as its central player. FAK gets phosphorylated and in turn associates with tyrosine
kinases like PI3K and ERK. FAK also activates PI3K and ERK that serve as very crucial mediators of the signaling pathway leading
to induction of MMP-2 activity and resulting invasion of breast cancer cell, MCF-7.
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Keywords
Breast cancer, Focal Adhesion Kinase, Integrin, Matrix metalloproteinase, Metastasis, Signaling
Citation
Sen Triparna, Ganguly Kirat Kumar, Biswas Jaydip, Chatterjee Amitava. Focal Adhesion Kinase Induces Matrix Metalloproteinase-2 by Involving α5β1-Mediated Signaling in Breast Cancer Cell, MCF-7. Acta Medica International. 2015 Jan-Jun: 2(1): 29-39.