Transcriptomics

Dataset Information

0

Genome functional screening identifies GAB2 as a key promoter of anchorage independence in normal and neoplastic cells


ABSTRACT: Acquisition of independence from anchorage to the extracellular matrix is a critical event for onset and progression of solid cancers. To identify and characterize new genes conferring anchorage independence, we transduced MCF10A human normal breast cells with a retroviral cDNA expression library and selected them by growth in suspension. Microarray analysis targeted on library-derived transcripts revealed robust and reproducible enrichment, after selection, of cDNAs encoding the scaffolding adaptor Gab2. Gab2 was confirmed to strongly promote anchorage-independent growth when overexpressed. Interestingly, downregulation by RNAi of endogenous Gab2 in neoplastic cells did not affect their adherent growth, but abrogated their growth in soft agar. Gab2-driven anchorage independence was found to specifically involve activation of the Src-Stat3 signaling axis. A transcriptional “signature” of 205 genes was obtained from GAB2-transduced, anchorage-independent MCF10A cells, and found to contain two main functional modules, respectively controlling proliferation and cell adhesion/migration/invasion. Extensive validation on breast cancer datasets showed that the Gab2-signature provides a robust prognostic classifier for breast cancer metastatic relapse, largely independent from existing clinical and genomic indicators and from estrogen receptor status. This work highlights a pivotal role for GAB2 and its transcriptional targets in anchorage-independent growth and breast cancer metastatic progression.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE18237 | GEO | 2009/10/21

SECONDARY ACCESSION(S): PRJNA119625

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2009-04-10 | E-GEOD-15161 | biostudies-arrayexpress
2009-04-10 | GSE15026 | GEO
2021-01-31 | GSE152312 | GEO
2009-04-10 | GSE15161 | GEO
2008-06-10 | GSE11721 | GEO
2009-04-10 | E-GEOD-15026 | biostudies-arrayexpress
2020-06-23 | GSE130650 | GEO
2008-07-29 | GSE12215 | GEO
2008-07-29 | E-GEOD-12215 | biostudies-arrayexpress
2010-08-21 | GSE23734 | GEO