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侵袭性肺癌中的上皮-间质转化

Epithelial Mesenchymal Transition in Aggressive Lung Cancers.

作者信息

Mittal Vivek

机构信息

Department of Cardiothoracic Surgery, Neuberger Berman Foundation Lung Cancer Center, New York, NY, 10065, USA.

Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.

出版信息

Adv Exp Med Biol. 2016;890:37-56. doi: 10.1007/978-3-319-24932-2_3.

Abstract

The progression of a cancer cell into a metastatic entity contributes to more than 90 % of cancer related deaths. Therefore, the prevention and treatment of metastasis is an unmet clinical need. Epithelial to mesenchymal transition (EMT) is an evolutionary conserved developmental program, which is induced during cancer progression and contributes to metastatic colonization. EMT endows metastatic properties upon cancer cells by enhancing mobility, invasion, and resistance to apoptotic stimuli. Furthermore, EMT-derived tumor cells acquire stem cell properties and exhibit therapeutic resistance. The disseminated tumor cells recruited to distant organs are suggested to subsequently undergo an EMT reversion through mesenchymal to epithelial transition (MET), necessary for efficient colonization and macrometastasis. A major focus of cancer research is to determine the cellular and molecular mechanisms underlying EMT/MET in tumor invasion, dissemination and metastasis. In this chapter, we will focus on the contribution of the EMT signaling pathways in lung cancer progression, cancer stem cells and acquired resistance to EGFR tyrosine kinase inhibitors and chemotherapy. We will also discuss the potential of targeting EMT pathways as an attractive strategy for the treatment of lung cancer.

摘要

癌细胞发展为转移实体导致了超过90%的癌症相关死亡。因此,预防和治疗转移是一项尚未满足的临床需求。上皮-间质转化(EMT)是一个进化上保守的发育程序,在癌症进展过程中被诱导,并促进转移定植。EMT通过增强迁移、侵袭和对凋亡刺激的抗性赋予癌细胞转移特性。此外,EMT衍生的肿瘤细胞获得干细胞特性并表现出治疗抗性。被招募到远处器官的播散肿瘤细胞随后被认为会通过间质-上皮转化(MET)经历EMT逆转,这是有效定植和大转移所必需的。癌症研究的一个主要重点是确定肿瘤侵袭、播散和转移中EMT/MET的细胞和分子机制。在本章中,我们将重点关注EMT信号通路在肺癌进展、癌症干细胞以及对EGFR酪氨酸激酶抑制剂和化疗的获得性抗性中的作用。我们还将讨论靶向EMT通路作为一种有吸引力的肺癌治疗策略的潜力。

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