Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl.
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.
Department of Surgical Oncology and Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.
Xinmiao
X
Yu
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Xiupeng
X
Zhang
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Yong
Y
Zhang
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Guiyang
G
Jiang
Department of Surgical Oncology and Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.
Xiaoyun
X
Mao
Department of Surgical Oncology and Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.
Feng
F
Jin
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003600:Cytosol / Q000378:metabolism*; D000072261:Dishevelled Proteins; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D062793:Occludin / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D000071250:Snail Family Transcription Factors; C569042:TJP1 protein, human; C555652:TMEM88 protein, human; D014157:Transcription Factors; D062826:Zonula Occludens-1 Protein
Snail; TMEM88; cytosolic; invasion; triple-negative breast cancer