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Src、化学抗性与上皮-间质转化:它们有关联吗?

Src, chemoresistance and epithelial to mesenchymal transition: are they related?

作者信息

Shah Ami N, Gallick Gary E

机构信息

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Anticancer Drugs. 2007 Apr;18(4):371-5. doi: 10.1097/CAD.0b013e32801265d7.

Abstract

The Src family of nonreceptor tyrosine kinases regulates numerous cellular processes, including proliferation, differentiation, migration, survival and angiogenesis. In solid tumors, Src is frequently aberrantly active, and promotes tumor progression and metastasis. Although multiple Src functions may contribute to metastasis, recently Src has been shown to play a role in epithelial to mesenchymal transition. Increased Src activity promotes this process and inhibition of Src suppresses epithelial to mesenchymal transition. Although the molecular events causing epithelial to mesenchymal transition are becoming well defined, the processes in tumor cells that trigger the onset of this phenotype remain unclear. Recent studies have associated epithelial to mesenchymal transition with the development of chemoresistance. Src has also been shown to be involved in chemoresistance of cancer cells. The activation of Src in chemoresistant cells is related to an increase in motility, invasiveness and detachment, all phenotypes characteristic both of Src activation and of epithelial to mesenchymal transition. This review focuses on upregulation of Src in cancer as it relates to chemoresistance and epithelial to mesenchymal transition.

摘要

非受体酪氨酸激酶的Src家族调节众多细胞过程,包括增殖、分化、迁移、存活和血管生成。在实体瘤中,Src经常异常激活,并促进肿瘤进展和转移。尽管Src的多种功能可能有助于转移,但最近研究表明Src在上皮-间质转化中发挥作用。Src活性增加促进这一过程,而抑制Src则抑制上皮-间质转化。尽管导致上皮-间质转化的分子事件正逐渐明确,但肿瘤细胞中触发这种表型发生的过程仍不清楚。最近的研究将上皮-间质转化与化疗耐药性的发展联系起来。Src也已被证明与癌细胞的化疗耐药性有关。化疗耐药细胞中Src的激活与运动性、侵袭性和脱离增加有关,所有这些表型都是Src激活和上皮-间质转化的特征。本综述重点关注癌症中Src的上调与化疗耐药性和上皮-间质转化的关系。

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