Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells
Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells
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DOI：
10.1038/sj.onc.1210035
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发表时间：
2007-04-12
期刊：
影响因子：
8
通讯作者：
Mehta, K.
中科院分区：
文献类型：
--
作者：
Mangala, L. S.;Fok, J. Y.;Mehta, K.
远处转移常见于乳腺癌患者，也是这些患者癌症相关死亡的主要原因。目前，人们对乳腺癌细胞转移表型形成的机制知之甚少。我们以前发现转移性乳腺癌细胞表达高水平的组织转谷氨酰胺酶(TG2)，但没有建立TG2与转移之间的直接联系。在这项研究中，我们假设TG2在赋予乳腺癌细胞转移表型方面起作用。这些结果表明，TG2在乳腺癌细胞中的表达增加有助于提高其存活率、侵袭力和运动能力。我们进一步发现，在转移性乳腺癌MDA-MB231细胞中，TG2蛋白存在于细胞表面，与整合素β1、β4和β5密切相关。小干扰RNA可抑制内源性TG2的下调。粘连蛋白(FN)介导细胞的附着、存活和侵袭。相反，TG2的异位表达增加了乳腺癌细胞的侵袭性和对FN涂层表面的附着。我们认为TG2在乳腺癌细胞中的表达在乳腺癌细胞转移表型的形成中起重要作用。
Distant metastasis is frequently observed in patients with breast cancer and is a major cause of cancer-related deaths in these patients. Currently, very little is known about the mechanisms that underlie the development of the metastatic phenotype in breast cancer cells. We previously found that metastatic breast cancer cells express high levels of tissue transglutaminase (TG2), but established no direct link between TG2 and metastasis. In this study, we hypothesized that TG2 plays a role in conferring the metastatic phenotype to breast cancer cells. The results obtained suggested that increased expression of TG2 in breast cancer cells contributes to their increased survival, invasion and motility. We further found that TG2 protein in a metastatic breast cancer MDA-MB231 cells was present on the cell surface in close association with integrins beta 1, beta 4 and beta 5. Downregulation of endogenous TG2 by small interfering RNA inhibited. bronectin (Fn)mediated cell attachment, survival and invasion. Conversely, ectopic expression of TG2 augmented invasion of breast cancer cells and attachment to Fn-coated surfaces. We conclude that TG2 expression in breast cancer cells plays an important role in the development of the metastatic phenotype.