Universität zu Köln

Schuette, Ute, Bisht, Savita, Heukamp, Lukas C., Kebschull, Moritz ORCID: 0000-0003-1863-0679, Florin, Alexandra, Haarmann, Jens, Hoffmann, Per, Bendas, Gerd, Buettner, Reinhard, Brossart, Peter and Feldmann, Georg (2014). Hippo Signaling Mediates Proliferation, Invasiveness, and Metastatic Potential of Clear Cell Renal Cell Carcinoma. Transl. Oncol., 7 (2). S. 309 - 322. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1936-5233

Full text not available from this repository.

Abstract

Recent work has identified dysfunctional Hippo signaling to be involved in maintenance and progression of various human cancers, although data on clear cell renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and metastatic potential. Nuclear overexpression of the Hippo target Yes-associated protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was particularly prominent at the tumor margins and highlighted neoplastic cells invading the tumor-adjacent stroma. Short hairpin RNA-mediated knockdown of YAP significantly inhibited proliferation, migration, and anchorage-independent growth of ccRCC cells in soft agar and led to significantly reduced murine xenograft growth. Microarray analysis of YAP knockdown versus mock-transduced ccRCC cells revealed downregulation of endothelin 1, endothelin 2, cysteine-rich, angiogenic inducer, 61 (CYR61), and c-Myc in ccRCC cells as well as up-regulation of the cell adhesion molecule cadherin 6. Signaling pathway impact analysis revealed activation of the p53 signaling and cell cycle pathways as well as inhibition of mitogen-activated protein kinase signaling on YAP down-regulation. Our data suggest CYR61 and c-Myc as well as signaling through the endothelin axis as bona fide downstream effectors of YAP and establish aberrant Hippo signaling as a potential therapeutic target in ccRCC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schuette, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Bisht, Savita UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kebschull, Moritz UNSPECIFIED orcid.org/0000-0003-1863-0679 UNSPECIFIED Florin, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Haarmann, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Per UNSPECIFIED UNSPECIFIED UNSPECIFIED Bendas, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Brossart, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Feldmann, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443036
DOI:	10.1016/j.tranon.2014.02.005
Journal or Publication Title:	Transl. Oncol.
Volume:	7
Number:	2
Page Range:	S. 309 - 322
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1936-5233
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language YES-ASSOCIATED PROTEIN; ENDOTHELIN AXIS; GENE-EXPRESSION; CADHERIN EXPRESSION; MESSENGER-RNA; EMERGING ROLE; SIZE-CONTROL; CANCER; PROMOTES; PATHWAY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44303