CD74 interacts with CD44 and enhances tumorigenesis and metastasis via RHOA-mediated cofilin phosphorylation in human breast cancer cells
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Zhiyong Liu1, Shuzhou Chu2, Shun Yao1, Yu Li1, Songqing Fan2, Xiaoyang Sun1, Ling Su1, Xiangguo Liu1
1Shandong University School of Life Sciences, Jinan, China
2Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China
Xiangguo Liu, email: firstname.lastname@example.org
Ling Su, email: email@example.com
Keywords: CD74, CFL1, CD44, RHOA
Received: July 10, 2016 Accepted: September 07, 2016 Published: September 10, 2016
CD74, also known as Ii, was initially considered to participate primarily in antigen presentation. Subsequent studies have shown that CD74 is highly expressed in various types of tumor cells and has multiple roles in a variety of biological processes. CD74 is thought to promote breast cancer metastasis, but the molecular mechanism remains elusive. In the present study, our results showed that CD74 was more highly expressed on the membrane and in the cytoplasm of breast cancer tissues than in control breast tissues. Consistently, CD74 downregulation reduced MDA-MB-231 cell invasion and migration and suppressed protrusions in breast cancer cells. Moreover, CD74 overexpression promoted the phosphorylation of the actin-severing protein cofilin (CFL1), resulting in actin polymerization in breast cancer cells. CD44 was required for the up-regulation of CFL1 phosphorylation by CD74 because CD44 knockdown downregulated CD74-induced CFL1 phosphorylation, while CD74 overexpression could not rescue CFL1 phosphorylation. Moreover, RHOA is necessary for CFL1 phosphorylation and cell migration induced by CD74 in breast cancer cells. Our findings highlight the critical role of CD74 in breast cancer metastasis. New drugs and antibodies targeting CD74 may be effective strategies for breast cancer therapy.
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