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

Research output: Contribution to journalReview articlepeer-review


>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
StatePublished - 1 Oct 2016


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


Dive into the research topics of 'Oncogenic KRAS signaling and YAP1/β-catenin: Similar cell cycle control in tumor initiation'. Together they form a unique fingerprint.

Cite this