@article{52ace157eefe4314a93f0ac0e4f6cf3c,
title = "Oncogenic KRAS signaling and YAP1/β-catenin: Similar cell cycle control in tumor initiation",
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.",
keywords = "Cancer, Cellular pathways, Drug resistance, Hippo, K-Ras, Myc, Proliferation, WNT",
author = "Ruth Nussinov and Tsai, {Chung Jung} and Hyunbum Jang and Tam{\'a}s Korcsm{\'a}ros and Peter Csermely",
note = "Publisher Copyright: {\textcopyright} 2016 Ruth Nussinov",
year = "2016",
month = oct,
day = "1",
doi = "10.1016/j.semcdb.2016.04.001",
language = "אנגלית",
volume = "58",
pages = "79--85",
journal = "Seminars in Cell and Developmental Biology",
issn = "1084-9521",
publisher = "Elsevier Ltd.",
}