Oncotarget

Research Papers:

Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl

Xinmiao Yu _, Xiupeng Zhang, Yong Zhang, Guiyang Jiang, Xiaoyun Mao and Feng Jin

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Oncotarget. 2015; 6:25034-25045. https://doi.org/10.18632/oncotarget.4379

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Abstract

Xinmiao Yu1, Xiupeng Zhang2, Yong Zhang2, Guiyang Jiang2, Xiaoyun Mao1, Feng Jin1

1Department of Surgical Oncology and Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China

2Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China

Correspondence to:

Feng Jin, e-mail: [email protected]

Keywords: cytosolic, TMEM88, triple-negative breast cancer, invasion, snail

Received: February 04, 2015     Accepted: June 19, 2015     Published: June 29, 2015

ABSTRACT

TMEM88, a newly discovered protein localized on the cell membrane, inhibits canonical Wnt signaling. Immunohistochemic alanalysis of 139 breast cancers pecimens(64 triple-negative cancers and 75 non-triple-negative cancers) indicated that TMEM88 is expressed at significantly higher levels in breast cancer tissues (71.22%, 99/139) than in normal breast tissues (11.4%, 4/35; p < 0.001). The cytosolic and nuclear expression rates of TMEM88 were 57.81% and 9.37% in triple-negative and 52% and 33.33% (p = 0.5 and p = 0.001) in the non-triple-negative breast cancer tissues, respectively. Western blot analyses indicated that TMEM88 promoted Snail expression and inhibited Zo-1 and Occludin expression by interacting with dishevelled (Dvl) proteins, thereby stimulating invasion and metastasis in breast cancer. While cytosolic TMEM88 did not affect canonical Wnt signaling, cytosolic localization of this protein was positively correlated with both advanced TNM stage (p = 0.038 and p < 0.001) and lymph node metastasis (p = 0.01 and p = 0.002) in all and triple-negative specimens, respectively, and stimulated cell invasion by interacting with Dvls. Meanwhile, nuclear localization of TMEM88 was negatively correlated with lymph node metastasis (p = 0.046). Lastly, the increased prevalence of TMEM88 nuclear localization observed in non-triple-negative, compared to triple-negative tissues, suggests that the biological roles of TMEM88 differ depending on the subcellular localization.


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