CD44 targets Na(+)/H(+) exchanger 1 to mediate MDA-MB-231 cells' metastasis via the regulation of ERK1/2.
CD44 targets Na(+)/H(+) exchanger 1 to mediate MDA-MB-231 cells' metastasis via the regulation of ERK1/2.
复制标题
DOI：
10.1038/bjc.2013.809
复制
发表时间：
2014-02-18
影响因子：
8.8
通讯作者：
Pang, T.
中科院分区：
文献类型：
--
作者：
Chang, G.;Wang, J.;Zhang, H.;Zhang, Y.;Wang, C.;Xu, H.;Zhang, H.;Lin, Y.;Ma, L.;Li, Q.;Pang, T.
CD44是一种在多种细胞和组织中表达的跨膜糖蛋白，与肿瘤转移有关。但CD44介导的肿瘤细胞转移的分子机制仍有待阐明。通过免疫荧光测定CD44的下调。此外，通过伤口愈合和跨孔实验检测乳腺癌细胞的运动性。然后用BALB/c裸鼠进行组织学检测CD44沉默的MDA-MB-231细胞的自发转移。在两种乳腺癌细胞中发现 CD44 与 Na+/H+ 交换异构体 1 (NHE1) 呈正相关。 CD44下调可抑制MDA-MB-231细胞的转移和Na+/H+交换器1的表达。此外，CD44过表达上调MCF-7细胞的转移，但升高的转移能力随后被Cariporide抑制。有趣的是，在这些过程中，只有p-ERK1/2被CD44下调所抑制，基质金属蛋白酶的表达和MDA-MB-231细胞的转移能力被MEK1抑制剂PD98059极大地抑制，甚至与Cariporide具有协同作用。此外，CD44 下调可抑制乳腺肿瘤生长和自发性肺转移。综上所述，这项工作表明CD44通过调节NHE1表达来调节乳腺癌细胞的转移，这可以作为乳腺癌治疗的新策略。
CD44, a transmembrane glycoprotein expressed in a variety of cells and tissues, has been implicated in tumour metastasis. But the molecular mechanisms of CD44-mediated tumour cell metastasis remain to be elucidated. The downregulation of CD44 was determined by immunofluorescence. Moreover, the motility of breast cancer cells was detected by wound-healing and transwell experiments. Then the spontaneous metastasis of CD44-silenced MDA-MB-231 cells was tested by histology with BALB/c nude mice. A positive correlation between CD44 and Na+/H+ exchanger isoform 1 (NHE1) was found in two breast cancer cells. CD44 downregulation could inhibit the metastasis of MDA-MB-231 cells and the expressions of Na+/H+ exchanger 1. Moreover, CD44 overexpression upregulated the metastasis of MCF-7 cells, but the elevated metastatic ability was then inhibited by Cariporide. Interestingly, during these processes only the p-ERK1/2 was suppressed by CD44 downregulation and the expression of matrix metalloproteinases and metastatic capacity of MDA-MB-231 cells were greatly inhibited by the MEK1 inhibitor PD98059, which even had a synergistic effect with Cariporide. Furthermore, CD44 downregulation inhibits breast tumour outgrowth and spontaneous lung metastasis. Taken together, this work indicates that CD44 regulates the metastasis of breast cancer cells through regulating NHE1 expression, which could be used as a novel strategy for breast cancer therapy.
登录
查看更多内容
膜型1基质金属蛋白酶切割CD44并促进细胞迁移。
影响因子：
7.8
作者：
Kajita, M;Itoh, Y;Chiba, T;Mori, H;Okada, A;Kinoh, H;Seiki, M
通讯作者：
Seiki, M
影响因子：
4.8
作者：
Midgley, Adam C.;Rogers, Mathew;Steadman, Robert
通讯作者：
Steadman, Robert
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ
影响因子：
2.5
作者：
Bourguignon, LYW
通讯作者：
Bourguignon, LYW