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RASSF1A-Mediated Suppression of Estrogen Receptor Alpha (ERα)-Driven Breast Cancer Cell Growth Depends on the Hippo-Kinases LATS1 and 2

Roßwag, Sven; Sleeman, Jonathan P. ORCID iD icon; Thaler, Sonja

Abstract:

Around 70% of breast cancers express the estrogen receptor alpha (ERα). This receptor is of central importance for breast cancer development and estrogen-dependent tumor growth. However, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast carcinogenesis are complex and not fully understood. In previous work, we have demonstrated that the tumor suppressor RASSF1A suppresses estrogen-dependent growth of breast cancer cells through a complex network that keeps ERα expression and function under control. We observed that RASSF1A mediates the suppression of ERα expression through modulation of the Hippo effector Yes-associated protein 1 (YAP1) activity. Here we report that RASSF1A-mediated alteration of YAP1 depends on the Hippo-kinases LATS1 and LATS2. Based on these results, we conclude that inactivation of RASSF1A causes changes in the function of the Hippo signaling pathway and altered activation of YAP1, and as a consequence, increased expression and function of ERα. Thus, the inactivation of RASSF1A might constitute a fundamental event that supports the initiation of ERα-dependent breast cancer. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000142042
Veröffentlicht am 18.01.2022
Originalveröffentlichung
DOI: 10.3390/cells10112868
Scopus
Zitationen: 1
Web of Science
Zitationen: 3
Dimensions
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 11.2021
Sprache Englisch
Identifikator ISSN: 2073-4409
KITopen-ID: 1000142042
HGF-Programm 47.14.02 (POF IV, LK 01) Information Storage and Processing in the Cell Nucleus
Erschienen in Cells
Verlag MDPI
Band 10
Heft 11
Seiten Art. Nr.: 2868
Vorab online veröffentlicht am 24.10.2021
Schlagwörter RASSF1A; ER+ breast cancer; activation of LATS1/2; inhibition of YAP1
Nachgewiesen in Dimensions
Scopus
Web of Science
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