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Int J Cancer. 2018 Aug 15;143(4):921-930. doi: 10.1002/ijc.31374. Epub 2018 Mar 30.

Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.

Author information

1
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
2
Department of Dermatology, Duke University Medical Center, Durham, NC.
3
Cancer Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 has also non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remain to be defined clearly. In our study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared to parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastasis.

KEYWORDS:

caspase-3; chemotherapy; colon cancer; invasion; metastasis; radiotherapy

PMID:
29524226
PMCID:
PMC6204286
[Available on 2019-08-15]
DOI:
10.1002/ijc.31374
[Indexed for MEDLINE]

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