CD74 interacts with CD44 and enhances tumorigenesis and metastasis via RHOA-mediated cofilin phosphorylation in human breast cancer cells.
CD74 interacts with CD44 and enhances tumorigenesis and metastasis via RHOA-mediated cofilin phosphorylation in human breast cancer cells.
复制标题
CD74 与 CD44 相互作用，通过 RHOA 介导的丝切蛋白磷酸化增强人乳腺癌细胞中的肿瘤发生和转移
DOI：
10.18632/oncotarget.11945
复制
发表时间：
2016-10-18
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Liu Z;Chu S;Yao S;Li Y;Fan S;Sun X;Su L;Liu X
CD 74，也称为Ii，最初被认为主要参与抗原呈递。随后的研究表明，CD 74在各种类型的肿瘤细胞中高度表达，并在多种生物学过程中发挥多种作用。CD 74被认为是促进乳腺癌转移的分子机制，但仍不清楚。在本研究中，我们的研究结果表明，CD 74是更高的表达在膜和细胞质中的乳腺癌组织比对照乳腺组织。一致地，CD 74下调减少了MDA-MB-231细胞的侵袭和迁移，并抑制了乳腺癌细胞的突起。此外，CD 74过表达促进肌动蛋白切割蛋白cofilin（CFL 1）的磷酸化，导致乳腺癌细胞中肌动蛋白聚合。CD 74上调CFL 1磷酸化需要CD 44，因为CD 44敲低下调CD 74诱导的CFL 1磷酸化，而CD 74过表达不能拯救CFL 1磷酸化。此外，在乳腺癌细胞中，RHOA对于CD 74诱导的CFL 1磷酸化和细胞迁移是必需的。我们的研究结果强调了CD 74在乳腺癌转移中的关键作用。靶向CD 74的新药物和抗体可能是乳腺癌治疗的有效策略。
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.