ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells

João Agostinho Machado-Neto; Mariana Lazarini; Patricia Favaro; Gilberto Carlos Franchi Jr; Alexandre Eduardo Nowill; Sara Teresinha Olalla Saad; Fabiola Traina

doi:10.1016/j.yexcr.2014.04.004

ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells

Exp Cell Res. 2014 Jun 10;324(2):137-45. doi: 10.1016/j.yexcr.2014.04.004. Epub 2014 Apr 12.

Authors

João Agostinho Machado-Neto¹, Mariana Lazarini¹, Patricia Favaro², Gilberto Carlos Franchi Jr³, Alexandre Eduardo Nowill³, Sara Teresinha Olalla Saad¹, Fabiola Traina⁴

Affiliations

¹ Hematology and Hemotherapy Center, University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
² Hematology and Hemotherapy Center, University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil; Department of Biological Sciences, Federal University of São Paulo, Diadema, São Paulo, Brazil.
³ Integrated Center for Childhood Onco-Hematological Investigation, University of Campinas, Campinas, São Paulo, Brazil.
⁴ Hematology and Hemotherapy Center, University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil; Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil. Electronic address: ftraina@fmrp.usp.br.

PMID: 24726915
DOI: 10.1016/j.yexcr.2014.04.004

Abstract

ANKHD1 is a multiple ankyrin repeat containing protein, recently identified as a novel member of the Hippo signaling pathway. The present study aimed to investigate the role of ANKHD1 in DU145 and LNCaP prostate cancer cells. ANKHD1 and YAP1 were found to be highly expressed in prostate cancer cells, and ANKHD1 silencing decreased cell growth, delayed cell cycle progression at the S phase, and reduced tumor xenograft growth. Moreover, ANKHD1 knockdown downregulated YAP1 expression and activation, and reduced the expression of CCNA2, a YAP1 target gene. These findings indicate that ANKHD1 is a positive regulator of YAP1 and promotes cell growth and cell cycle progression through Cyclin A upregulation.

Keywords: ANKHD1; Cell cycle; Hippo pathway; MASK; Prostate cancer; YAP1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Cycle / genetics*
Cell Line, Tumor
Cyclin A / genetics
Cyclin A / metabolism
Gene Expression Regulation, Neoplastic*
HeLa Cells
Hippo Signaling Pathway
Humans
K562 Cells
Male
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Phosphoproteins / genetics*
Phosphoproteins / metabolism
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
Protein Serine-Threonine Kinases / metabolism
RNA-Binding Proteins / physiology*
Signal Transduction / genetics
Transcription Factors
Transcriptional Activation
YAP-Signaling Proteins

Substances

ANKHD1 protein, human
Adaptor Proteins, Signal Transducing
Cyclin A
Phosphoproteins
RNA-Binding Proteins
Transcription Factors
YAP-Signaling Proteins
YAP1 protein, human
Protein Serine-Threonine Kinases