CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis.
Hepatocellular carcinoma (HCC) is one of the most malignant tumors with high rate of recurrence and metastasis. Coiled-coil domain-containing protein 178 (CCDC178) has been reported to be mutated in HCC, whereas its role in physiological and pathologic process, including in human cancer, remains largely unknown. Here, we found that CCDC178 is upregulated in HCC tissues and its overexpression is correlated with pathological stage (P=0.003). CCDC178 deficiency reduced the anchorage-independent growth and anoikis resistance of HCC cells, and inhibited the HCC metastasis in vivo. Mechanistically, CCDC178 associated with BRCA1-associated protein 2 (BRAP2), a negative regulator of extracellular signal-regulated kinase (ERK) pathway, and promoted its degradation. Moreover, CCDC178 deficiency impaired the ERK activation, which is dependent on BRAP2. In conclusion, we identify CCDC178 as a novel candidate oncogene involved in anoikis resistance and HCC metastasis, and raise the possibility that CCDC178 may be a new therapeutic target for HCC.
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Hu
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Zhao
Department of Oncology, The 401 Hospital of PLA, Qingdao, People's Republic of China.
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Wei
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Zhu
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Song
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Wang
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Yu
The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People's Republic of China.
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Wu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D023102:Anoikis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D015854:Up-Regulation
C000622898:CCDC178 protein, human; D003598:Cytoskeletal Proteins