The Effect of Adipocyte-Secreted Factors in Activating Focal Adhesion Kinase-Mediated Cell Signaling Pathway towards Metastasis in Breast Cancer Cells

Abstract

Obesity-associated perturbations in the normal secretion of adipocytokines from white adipocytes can drive the metastatic progression of cancer. However, the association between obesity-induced changes in secretory factors of white adipocytes and subsequent transactivation of the downstream effector proteins impacting metastasis in breast cancer cells remains unclear. Focal adhesion kinase, a cytoplasmic signal transducer, regulates the biological phenomenon of metastasis by activating downstream targets such as beta-catenin and MMP9. Thus, the possible role of phosphorylated FAK in potentiating cancer cell migration was investigated. To elucidate this potential relationship, MCF7 (ER+), MDA-MB-231 (Triple Negative) breast cancer cells, and MCF-10A non-tumorigenic breast cells were exposed to in vitro murine adipocyte-conditioned medium derived from 3T3-L1 MBX cells differentiated to obesity with fatty acid supplementation. Our results show that the conditioned medium derived from these obese adipocytes enhanced motility and invasiveness of breast cancer cells. Importantly, no such changes were observed in the non-tumorigenic breast cells. Our results also show that increased FAK autophosphorylation was followed by increased expression of beta-catenin and MMP9 in the breast cancer cells when exposed to obese adipocyte-conditioned medium, but not in the MCF10A cells. These results indicate that adipocyte-derived secretory factors induced FAK activation through phosphorylation. This in turn increased breast cancer cell migration and invasion by activating its downstream effector proteins beta-catenin and MMP9.

Description

© 2023 by the authors. cc-by

Keywords

3T3-L1 MBX, adipocytokine, breast cancer cells, conditioned medium, FAK, in vitro, non-tumorigenic breast cells, obesity, signal transduction

Citation

Mubtasim, N., & Gollahon, L.. 2023. The Effect of Adipocyte-Secreted Factors in Activating Focal Adhesion Kinase-Mediated Cell Signaling Pathway towards Metastasis in Breast Cancer Cells. International Journal of Molecular Sciences, 24(23). https://doi.org/10.3390/ijms242316605

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