Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers

Emily N. Arner; Wenting Du; Rolf A. Brekken

doi:10.3389/fonc.2019.01049

Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers

Emily N. Arner, Wenting Du, Rolf A. Brekken

Research output: Contribution to journal › Review article › peer-review

22 Scopus citations

Abstract

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.

Original language	English (US)
Article number	1049
Journal	Frontiers in Oncology
Volume	9
DOIs	https://doi.org/10.3389/fonc.2019.01049
State	Published - Oct 11 2019

Keywords

AXL
EMT
KRAS
TBK1
drug resistance
metastasis

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3389/fonc.2019.01049

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title = "Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers",

abstract = "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.",

keywords = "AXL, EMT, KRAS, TBK1, drug resistance, metastasis",

author = "Arner, {Emily N.} and Wenting Du and Brekken, {Rolf A.}",

note = "Funding Information: We apologize to the colleagues whose work could not be included due to space restrictions. We thank the members of the Brekken laboratory for critical discussion and thank Dave Primm for editorial assistance. Funding. The work was supported by NIH grants R01 CA192381 and U54 CA210181 Project 2 to RB and support from the Effie Marie Cain Scholarship in Angiogenesis Research. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2019 Arner, Du and Brekken.",

year = "2019",

month = oct,

day = "11",

doi = "10.3389/fonc.2019.01049",

language = "English (US)",

volume = "9",

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AU - Arner, Emily N.

AU - Du, Wenting

AU - Brekken, Rolf A.

N1 - Funding Information: We apologize to the colleagues whose work could not be included due to space restrictions. We thank the members of the Brekken laboratory for critical discussion and thank Dave Primm for editorial assistance. Funding. The work was supported by NIH grants R01 CA192381 and U54 CA210181 Project 2 to RB and support from the Effie Marie Cain Scholarship in Angiogenesis Research. Publisher Copyright: © Copyright © 2019 Arner, Du and Brekken.

PY - 2019/10/11

Y1 - 2019/10/11

N2 - 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.

AB - 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.

KW - AXL

KW - EMT

KW - KRAS

KW - TBK1

KW - drug resistance

KW - metastasis

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AN - SCOPUS:85074296089

SN - 2234-943X

VL - 9

JO - Frontiers in Oncology

JF - Frontiers in Oncology

M1 - 1049

ER -

Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers

Abstract

Keywords

ASJC Scopus subject areas

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