Oncogenic KRAS signaling and YAP1/β-catenin: Similar cell cycle control in tumor initiation

Ruth Nussinov*, Chung Jung Tsai, Hyunbum Jang, Tamás Korcsmáros, Peter Csermely

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

>Why are YAP1 and c-Myc often overexpressed (or activated) in KRAS-driven cancers and drug resistance? Here, we propose that there are two independent pathways in tumor proliferation: one includes MAPK/ERK and PI3K/A kt/mTOR; and the other consists of pathways leading to the expression (or activation) of YAP1 and c-Myc. KRAS contributes through the first. MYC is regulated by e.g. β-catenin, Notch and Hedgehog. We propose that YAP1 and ERK accomplish similar roles in cell cycle control, as do β-catenin and PI3K. This point is compelling, since the question of how YAP1 rescues K-Ras or B-Raf ablation has recently captured much attention, as well as the mechanism of resistance to PI3K inhibitors. The similarity in cell cycle actions of β-catenin and PI3K can also clarify the increased aggressiveness of lung cancer when both K-Ras and β-catenin operate. >Thus, we propose that the two pathways can substitute one another – or together amplify each other – in promoting proliferation. This new understanding of the independence and correspondence of the two pathways in cancer – MAPK/ERK and PI3K/Akt/mTOR; and YAP1 and c-Myc – provide a coherent and significant picture of signaling-driven oncogenic proliferation and may help in judicious, pathway-based drug discovery.

Original languageEnglish
Pages (from-to)79-85
Number of pages7
JournalSeminars in Cell and Developmental Biology
Volume58
DOIs
StatePublished - 1 Oct 2016

Funding

FundersFunder number
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010441
Frederick National Laboratory for Cancer Research
Nemzeti Kutatási Fejlesztési és Innovációs HivatalK 115378

    Keywords

    • Cancer
    • Cellular pathways
    • Drug resistance
    • Hippo
    • K-Ras
    • Myc
    • Proliferation
    • WNT

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