UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2019-10-01

Document Type

Article Postprint

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Cells | Enzymes and Coenzymes | Neoplasms

Abstract

Breast cancer is the most common invasive neoplasia, and the second leading cause of the cancer deaths in women worldwide. Mammary tumorigenesis is severely linked to obesity, one potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloprotease secretion, and invasion. We found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Interestingly, leptin promotes the activation of FAK through a Src and STAT3-dependent canonical pathway. Specific inhibitors of FAK, Src and STAT3 showed that the effect exerted by leptin in cell migration in breast cancer cells is dependent on these proteins. Moreover, we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9 and invasion in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.

Keywords

Leptin, FAK, Src, cell migration, metalloproteases, invasion, breast cancer

Rights and Permissions

Copyright: © 2019 The authors. Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI of Published Version

10.1530/EC-19-0442

Source

Endocr Connect. 2019 Oct 1. pii: EC-19-0442. doi: 10.1530/EC-19-0442. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Endocrine connections

Related Resources

Link to Article in PubMed

PubMed ID

31671408

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.