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Open Access Research article

MYBBP1A suppresses breast cancer tumorigenesis by enhancing the p53 dependent anoikis

Kensuke Akaogi1, Wakana Ono1, Yuki Hayashi1, Hiroyuki Kishimoto12 and Junn Yanagisawa12*

Author affiliations

1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki, 305-8577, Japan

2 Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba Science City, Ibaraki, 305-8577, Japan

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Citation and License

BMC Cancer 2013, 13:65  doi:10.1186/1471-2407-13-65

Published: 7 February 2013

Abstract

Background

Tumor suppressor p53 is mutated in a wide variety of human cancers and plays a critical role in anoikis, which is essential for preventing tumorigenesis. Recently, we found that a nucleolar protein, Myb-binding protein 1a (MYBBP1A), was involved in p53 activation. However, the function of MYBBP1A in cancer prevention has not been elucidated.

Methods

Relationships between MYBBP1A expression levels and breast cancer progression were examined using patient microarray databases and tissue microarrays. Colony formation, xenograft, and anoikis assays were conducted using cells in which MYBBP1A was either knocked down or overexpressed. p53 activation and interactions between p53 and MYBBP1A were assessed by immunoprecipitation and western blot.

Results

MYBBP1A expression was negatively correlated with breast cancer tumorigenesis. In vivo and in vitro experiments using the breast cancer cell lines MCF-7 and ZR-75-1, which expresses wild type p53, showed that tumorigenesis, colony formation, and anoikis resistance were significantly enhanced by MYBBP1A knockdown. We also found that MYBBP1A binds to p53 and enhances p53 target gene transcription under anoikis conditions.

Conclusions

These results suggest that MYBBP1A is required for p53 activation during anoikis; therefore, it is involved in suppressing colony formation and the tumorigenesis of breast cancer cells. Collectively, our results suggest that MYBBP1A plays a role in tumor prevention in the context of p53 activation.

Keywords:
Breast cancer; Tumorigenesis; Anoikis; p53; MYBBP1A