Dataset Information


Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells.

ABSTRACT: The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the ?aa25-45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms-uncoupling from upstream signals and splice isoform ratios-drive the activity of LYN in aggressive breast cancers.

SUBMITTER: Tornillo G 

PROVIDER: S-EPMC6315108 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4348968 | BioStudies
2010-01-01 | S-EPMC2869247 | BioStudies
2006-01-01 | S-EPMC1895506 | BioStudies
2013-01-01 | S-EPMC3703149 | BioStudies
2015-01-01 | S-EPMC4496232 | BioStudies
2014-01-01 | S-EPMC3936488 | BioStudies
2020-01-01 | S-EPMC7065279 | BioStudies
| S-EPMC3433855 | BioStudies
1999-01-01 | S-EPMC1220449 | BioStudies
1000-01-01 | S-EPMC2857081 | BioStudies