Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition

Chromatin modulators with antagonistic functions on epithelial-mesenchymal interconversion regulate common pan-cancer genes. Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Science advances Ročník 7; číslo 9
Hlavní autori:	Serresi, Michela, Kertalli, Sonia, Li, Lifei, Schmitt, Matthias Jürgen, Dramaretska, Yuliia, Wierikx, Jikke, Hulsman, Danielle, Gargiulo, Gaetano
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States American Association for the Advancement of Science 01.02.2021
Predmet:	Biochemistry Cancer SciAdv r-articles
ISSN:	2375-2548, 2375-2548
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	Chromatin modulators with antagonistic functions on epithelial-mesenchymal interconversion regulate common pan-cancer genes. Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling is believed to be an EMT driver, the molecular mechanisms underlying epithelial-mesenchymal interconversion are incompletely understood. Here, we show that the impact of chromatin regulators on EMT interconversion is broader than that of kinases. By combining pharmacological modulation of EMT, synthetic genetic tracing, and CRISPR interference screens, we uncovered a minority of kinases and several chromatin remodelers, writers, and readers governing homeostatic EMT in lung cancer cells. Loss of ARID1A, DOT1L, BRD2, and ZMYND8 had nondeterministic and sometimes opposite consequences on epithelial-mesenchymal interconversion. Together with RNAPII and AP-1, these antagonistic gatekeepers control chromatin of active enhancers, including pan-cancer-EMT signature genes enabling supraclassification of anatomically diverse tumors. Thus, our data uncover general principles underlying transcriptional control of cancer cell plasticity and offer a platform to systematically explore chromatin regulators in tumor-state–specific therapy.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2375-2548 2375-2548
DOI:	10.1126/sciadv.abd7974