Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1

Liu, Yanliang; Guo, Fengqin; Zhu, Xu; Guo, Wenyi; Fu, Tao; Wang, Weixing

doi:10.7150/jca.34233

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J Cancer 2020; 11(3):750-758. doi:10.7150/jca.34233 This issue Cite

Research Paper

Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1

Yanliang Liu¹, Fengqin Guo², Xu Zhu¹, Wenyi Guo¹, Tao Fu¹, Weixing Wang^1,3✉

1. Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
2. Department of Gynaecology and obstetrics II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
3. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China

Citation:

Liu Y, Guo F, Zhu X, Guo W, Fu T, Wang W. Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1. J Cancer 2020; 11(3):750-758. doi:10.7150/jca.34233. https://www.jcancer.org/v11p0750.htm

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Abstract

Background: Death domain-associated protein (DAXX) is a tumor suppressor and its loss has been found in a variety of cancer types. Dysregulation of DAXX is strongly correlated with cancer metastasis. However, the role and functions of DAXX in colorectal cancer (CRC) metastasis are not fully understood.

Methods: We validated the mRNA and protein expression of DAXX in CRC specimens and CRC cell lines using real-time reverse transcription-PCR and Western blot, respectively. The overexpression plasmids of ZEB1 and E-cadherin and the siRNAs for DAXX and ZEB1 knockdown were constructed to study the impact of these factors on cells. Wound-healing assay and Transwell assay were performed to examine the cell motility and cell migration and invasion abilities, respectively. Luciferase assay was performed to assess the E-cadherin promoter activity. Immunoprecipitation assay was performed to investigate the interaction between proteins. The rescue experiment was carried out to verify whether the effect of DAXX on E-cadherin expression is depended on ZEB1.

Results: DAXX expression was lower in liver metastases than in primary colon cancer tissues. Our results demonstrated that DAXX directly interacted with ZEB1 and suppressed its inhibitory effect on promoter activity of E-cadherin through a ZEB1-dependent manner, and thus suppresses the cell motility, migration, and invasion of CRC cell lines.

Conclusion: In sum, these findings supported that the loss of DAXX is associated with cancer cell metastases in CRC. ZEB1-mediated transcriptional suppression of E-cadherin is a possible mechanism. DAXX/ZEB-1 pathway could be a potential therapeutic target for preventing cancer metastasis in CRC.

Keywords: colorectal cancer, DAXX, E-cadherin, metastasis, ZEB1

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APA

Liu, Y., Guo, F., Zhu, X., Guo, W., Fu, T., Wang, W. (2020). Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1. Journal of Cancer, 11(3), 750-758. https://doi.org/10.7150/jca.34233.

ACS

Liu, Y.; Guo, F.; Zhu, X.; Guo, W.; Fu, T.; Wang, W. Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1. J. Cancer 2020, 11 (3), 750-758. DOI: 10.7150/jca.34233.

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CSE

Liu Y, Guo F, Zhu X, Guo W, Fu T, Wang W. 2020. Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1. J Cancer. 11(3):750-758.

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