CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis
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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Neoplastic cells can evade anoikis upon activation of ERK2 caused by cellular aggregation and consequent EGFR stabilization mediated by ERBB2, or degradation of the negative ERK2 regulator BRAP, which is favored by CCDC178.
“Neoplastic cells can evade anoikis upon activation of mitogen-activated protein kinase 1 (MAPK1; best known as ERK2) caused by cellular aggregation and consequent epidermal growth factor receptor (EGFR) stabilization mediated by erb-b2 receptor tyrosine kinase 2 (ERBB2) [237, 240], or degradation of the negative ERK2 regulator BRCA1-associated protein (BRAP), which is favored by coiled-coil domain”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [241]
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- Authors
- Hu, X., Zhao, Y., Wei, L., Zhu, B., Song, D., Wang, J., Yu, L., & Wu, J.
- Affiliations
- Fudan University (CN)
- People's Liberation Army 401 Hospital (CN)
- Venue
- Oncogene
- Published
- 2017-03-20
- Volume
- 36
- Issue
- 28
- Pages
- 4047-4059
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2602917813
- Cited by
- 54
- References
- 36
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 3
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Fudan University
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- hepatocellular carcinoma, metastasis, anoikis resistance, ERK signaling, anchorage-independent growth, protein degradation, therapeutic target
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Cell Adhesion, Cell Movement, Cytoskeletal Proteins, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Mice, Nude, Middle Aged, Neoplasm Metastasis, Signal Transduction, Up-Regulation, Gene Expression Regulation, Neoplastic, Anoikis, Cell Line, Tumor, Mice, HEK293 Cells
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