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CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis

Oncogene volume 36, pages 4047–4059 (2017)Cite this article

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Abstract

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.

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Abbreviations

CCDC178:

coiled-coil domain-containing 178

BRAP2:

BRCA1-associated protein

HCC:

hepatocellular carcinoma

PCR:

polymerase chain reaction

PAGE:

polyacrylamide gel electrophoresis

ERK:

extracellular signal-regulated kinases

EGF:

epidermal growth factor

CHX:

cycloheximide.

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Acknowledgements

We thank Yongjun Dang at School of Basic Medical Science, Fudan University for fruitful scientific discussions and sharing some reagents. This work was supported by National Key Research and Development Plan (2016YFC0902401to JW); the National Key Sci-Tech Special Project of China (2013ZX10002010-08 to JW) and the National Natural Science Foundation of China (81272250 and 81472619 to JW).

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Authors and Affiliations

  1. The State Key Laboratory of Genetic Engineering, Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, People’s Republic of China

    X Hu, Y Zhao, B Zhu, D Song, J Wang, L Yu & J Wu

  2. Department of Oncology, The 401 Hospital of PLA, Qingdao, People’s Republic of China

    L Wei

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  1. X Hu
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  2. Y Zhao
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  8. J Wu
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Corresponding author

Correspondence to J Wu.

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The authors declare no conflict of interest.

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Author contributions

XH performed most experiments. YZ, LW, BZ, DS, JJW and LY provided technical support for various assays. JW designed the experiments and wrote the manuscript. All the authors read and approved the final manuscript.

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Hu, X., Zhao, Y., Wei, L. et al. CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis. Oncogene 36, 4047–4059 (2017). https://doi.org/10.1038/onc.2017.10

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