RT Journal Article
SR Electronic
T1 Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.31.458283
DO 10.1101/2021.08.31.458283
A1 Alison E. Obr
A1 Yung-Jun Chang
A1 Virginia Ciliento
A1 Alexander Lemenze
A1 Krystopher Maingrette
A1 Joseph J. Bulatowicz
A1 Quan Shang
A1 Emily Gallagher
A1 Derek LeRoith
A1 Teresa L. Wood
YR 2021
UL http://biorxiv.org/content/early/2021/10/10/2021.08.31.458283.abstract
AB The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted gene correlation network analysis (WGCNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.Competing Interest StatementThe authors have declared no competing interest.