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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Colon Cancer | Primary research

PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

Authors: Zhengbin Chai, Li Wang, Yabing Zheng, Na Liang, Xiwei Wang, Yingying Zheng, Zhiwei Zhang, Chuanxi Zhao, Tingting Zhu, Chunyan Liu

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research.

Methods

Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo.

Results

CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells.

Conclusions

PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.
Appendix
Available only for authorised users
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Metadata
Title
PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer
Authors
Zhengbin Chai
Li Wang
Yabing Zheng
Na Liang
Xiwei Wang
Yingying Zheng
Zhiwei Zhang
Chuanxi Zhao
Tingting Zhu
Chunyan Liu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0999-3

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