2. Academic Validation
  3. Radiosensitivity of colorectal cancer and radiation-induced gut damages are regulated by gasdermin E

Radiosensitivity of colorectal cancer and radiation-induced gut damages are regulated by gasdermin E

  • Cancer Lett. 2022 Mar 31:529:1-10. doi: 10.1016/j.canlet.2021.12.034.
Gao Tan 1,  Chunjing Lin 2,  Chongyang Huang 2,  Bingxia Chen 2,  Jiaye Chen 2,  Yanqiang Shi 2,  Fachao Zhi 3
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 2 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 3 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
PMID: 34979164 DOI: 10.1016/j.canlet.2021.12.034
Abstract

Although radiotherapy is an important clinical option available for colorectal Cancer (CRC), its use is restricted due to low radiosensitivity of CRC and high toxicity to surrounding normal tissues. The purpose of this study is to investigate the molecular mechanism by which CRC is not sensitive to radiation and radiation causes toxicity to surrounding normal tissues. Here we found that GSDME was silenced in CRC but markedly expressed in their surrounding normal tissues. GSDME determines radiation-induced Pyroptosis in CRC cells and normal epithelial cells through the caspase-3-dependent pathway. GSDME expression sensitizes radioresistant CRC cells to radiation. In the homograft model, after radiation treatment, the tumor volume and weight were significantly decreased in GSDME-expressed homograft tumors compared to GSDME-knockout homograft tumors. On the mechanism, radiation induced GSDME-mediated Pyroptosis in CRC cells, which recruited and activated NK cells to enhance antitumor immunity. In addition, GSDME-knockout mice were protected from radiation-induced weight loss and tissue damages in the intestine, stomach, liver and pancreas compared to wild-type control littermates. In summary, we show that GSDME determines CRC radiosensitivity and radiation-related toxicity to surrounding normal tissues through caspase-3-dependent Pyroptosis. Our finding reveals a previously unrecognized link between radiation and Pyroptosis.

Keywords

Colorectal cancer; Gasdermin E; Pyroptosis; Radiotherapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12466
    98.0%, Caspase-3 Inhibitor