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

Publication ,  Journal Article
Zhou, M; Liu, X; Li, Z; Huang, Q; Li, F; Li, C-Y
Published in: Int J Cancer
August 15, 2018

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.

Duke Scholars

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2018

Volume

143

Issue

4

Start / End Page

921 / 930

Location

United States

Related Subject Headings

  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Humans
  • Gene Knockout Techniques
  • Epithelial-Mesenchymal Transition
  • Enzyme-Linked Immunosorbent Assay
  • Drug Resistance, Neoplasm
  • Colonic Neoplasms
 

Citation

APA
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ICMJE
MLA
NLM
Zhou, M., Liu, X., Li, Z., Huang, Q., Li, F., & Li, C.-Y. (2018). Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer, 143(4), 921–930. https://doi.org/10.1002/ijc.31374
Zhou, Min, Xinjian Liu, Zonghai Li, Qian Huang, Fang Li, and Chuan-Yuan Li. “Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.Int J Cancer 143, no. 4 (August 15, 2018): 921–30. https://doi.org/10.1002/ijc.31374.
Zhou M, Liu X, Li Z, Huang Q, Li F, Li C-Y. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer. 2018 Aug 15;143(4):921–30.
Zhou, Min, et al. “Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.Int J Cancer, vol. 143, no. 4, Aug. 2018, pp. 921–30. Pubmed, doi:10.1002/ijc.31374.
Zhou M, Liu X, Li Z, Huang Q, Li F, Li C-Y. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer. 2018 Aug 15;143(4):921–930.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2018

Volume

143

Issue

4

Start / End Page

921 / 930

Location

United States

Related Subject Headings

  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Humans
  • Gene Knockout Techniques
  • Epithelial-Mesenchymal Transition
  • Enzyme-Linked Immunosorbent Assay
  • Drug Resistance, Neoplasm
  • Colonic Neoplasms