Genetic dependencies associated with transcription factor activities in human cancer cell lines

被引：0

作者：

Thatikonda, Venu ^{[1
,4
]}

Supper, Verena ^{[1
]}

Wachter, Johannes ^{[1
]}

Kaya, Onur ^{[1
]}

Kombara, Anju ^{[1
]}

Bilgilier, Ceren ^{[1
]}

Ravichandran, Madhwesh C. ^{[1
]}

Lipp, Jesse J. ^{[1
]}

Sharma, Rahul ^{[3
]}

Badertscher, Lukas ^{[3
]}

Boghossian, Andrew S.

Rees, Matthew G. ^{[2
]}

Ronan, Melissa M.

Roth, Jennifer A.

Grosche, Sarah ^{[1
]}

Ller, Ralph A. Neumu euro ^{[1
]}

Mauri, Barbara Mair Federico ^{[1
]}

Popa, Alexandra ^{[1
]}

机构：

[1] Boehringer Ingelheim RCV GmbH & Co KG, Dr Boehringer Gasse 5-11, A-1120 Vienna, Austria

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Myllia Biotechnol GmbH, Kanal 27, A-1110 Vienna, Austria

[4] Exscientia GmbH, Siemensstr 89-OG3, A-1210 Vienna, Austria

来源：

CELL REPORTS | 2024年 / 43卷 / 05期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; HIPPO PATHWAY; SYNTHETIC LETHALITY; TUMOR-GROWTH; YAP; INHIBITOR; NETWORK; RNA; TAZ; VULNERABILITIES;

D O I：

10.1016/j.celrep.2024.114175

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell -line -selective anti -proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear -regression -based framework identifies 3,047 pan -cancer and 3,952 cancer -type -specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

引用

页数：26

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