Notch and mTOR Signaling Pathways Promote Human Gastric Cancer Cell Proliferation.

Notch and mTOR Signaling Pathways Promote Human Gastric Cancer Cell Proliferation. Neoplasia. 2019 May 23;21(7):702-712 Authors: Hibdon ES, Razumilava N, Keeley TM, Wong G, Solanki S, Shah YM, Samuelson LC Abstract Notch pathway signaling is known to promote gastric stem cell proliferation, and constitutive pathway activation induces gastric tumors via mTORC1 activation in mouse genetic models. The purpose of this study was to determine whether human gastric adenocarcinomas are similarly dependent on Notch and mTORC1 signaling for growth. Gene expression profiling of 415 human gastric adenocarcinomas in The Cancer Genome Atlas, and a small set of locally obtained gastric cancers showed enhanced expression of Notch pathway components, including Notch ligands, receptors and downstream target genes. Human gastric adenocarcinoma tissues and chemically induced mouse gastric tumors both exhibited heightened Notch and mTORC1 pathway signaling activity, as evidenced by increased expression of the NOTCH1 receptor signaling fragment NICD, the Notch target HES1, and the mTORC1 target phosphorylated S6 ribosomal protein. Pharmacologic inhibition of either Notch or mTORC1 signaling reduced growth of human gastric cancer cell lines, with combined pathway inhibition causing a further reduction in growth, suggesting that both pathways are activated to promote gastric cancer cell proliferation. Further, mTORC1 signaling was reduced after Notch inhibi...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research