A genetic interaction is inferred when mutations or deletions in separate genes, each of which alone causes a minimal phenotype, result in lethality when combined in the same cell under a given condition.

Publication

Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy.

Xiao T, Li W, Wang X, Xu H, Yang J, Wu Q, Huang Y, Geradts J, Jiang P, Fei T, Chi D, Zang C, Liao Q, Rennhack J, Andrechek E, Li N, Detre S, Dowsett M, Jeselsohn RM, Liu XS, Brown M

Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current ER-targeted therapies. Estrogen directly drives CSK expression in ER+ breast cancer. At low CSK levels, as is ... [more]

Proc. Natl. Acad. Sci. U.S.A. Dec. 31, 2017; 115(31);7869-7878 [Pubmed: 29987050]

Throughput

High Throughput

Ontology Terms

phenotype: growth abnormality (HP:0001507)
phenotype: viability (PATO:0000169)

Additional Notes

CRISPR GI screen
Cell Line:T47D
Experimental Setup: Timecourse, negative selection, viability
GIST: A-phenotypic negative genetic interaction
Library: Geckov2
Significance Threshold: FDR<0.05

Curated By

BioGRID

Interaction Summary

CSK

Gene Ontology Biological Process

Gene Ontology Molecular Function

identical protein binding [IPI]non-membrane spanning protein tyrosine kinase activity [IBA]protein C-terminus binding [TAS]protein binding [IPI]protein tyrosine kinase activity [TAS]receptor binding [IBA]

Gene Ontology Cellular Component

STOM