Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers

被引：26

作者：

Arner, Emily N. ^{[1
,2
]}

Du, Wenting ^{[1
,2
]}

Brekken, Rolf A. ^{[1
,2
,3
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Surg, Canc Biol Grad Program, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

来源：

FRONTIERS IN ONCOLOGY | 2019年 / 9卷

关键词：

EMT; KRAS; metastasis; TBK1; AXL; drug resistance; TO-MESENCHYMAL TRANSITION; RECEPTOR TYROSINE KINASE; PANCREATIC DUCTAL ADENOCARCINOMA; SIGNATURE PREDICTS RESISTANCE; SMALL-MOLECULE INHIBITION; KAPPA-B ACTIVATION; CELL-GROWTH; K-RAS; CHROMOSOMAL INSTABILITY; SIGNALING PATHWAY;

D O I：

10.3389/fonc.2019.01049

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cellular plasticity, a feature associated with epithelial-to-mesenchymal transition (EMT), contributes to tumor cell survival,migration, invasion, and therapy resistance. Phenotypic plasticity of the epithelium is a critical feature in multiple phases of human cancer in an oncogene- and tissue-specific context. Many factors can drive epithelial plasticity, including activating mutations in KRAS, which are found in an estimated 30% of all cancers. In this review, we will introduce cellular plasticity and its effect on cancer progression and therapy resistance and then summarize the drivers of EMT with an emphasis on KRAS effector signaling. Lastly, we will discuss the contribution of cellular plasticity to metastasis and its potential clinical implications. Understanding oncogenic KRAS cellular reprogramming has the potential to reveal novel strategies to control metastasis in KRAS-driven cancers.

引用

页数：15

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