RRC ID 52893
Author Mitsuda Y, Morita K, Kashiwazaki G, Taniguchi J, Bando T, Obara M, Hirata M, Kataoka TR, Muto M, Kaneda Y, Nakahata T, Liu PP, Adachi S, Sugiyama H, Kamikubo Y.
Title RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.
Journal Sci Rep
Abstract The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.
Volume 8(1)
Pages 6423
Published 2018-4-23
DOI 10.1038/s41598-018-24969-w
PII 10.1038/s41598-018-24969-w
PMID 29686309
PMC PMC5913281
MeSH Cell Line, Tumor Cell Proliferation Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors Core Binding Factor Alpha 2 Subunit / metabolism Core Binding Factor Alpha 2 Subunit / physiology* Dose-Response Relationship, Drug Humans Receptor, ErbB-2 / metabolism* SOS1 Protein / metabolism Signal Transduction / physiology* Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Up-Regulation
IF 3.998
Times Cited 14
DNA material pENTR4-H1tetOx1 (RDB07916) CS-RfA-ETV (RDB08020).