2. Academic Validation
  3. Fusobacterium nucleatum induces chemoresistance in colorectal cancer by inhibiting pyroptosis via the Hippo pathway

Fusobacterium nucleatum induces chemoresistance in colorectal cancer by inhibiting pyroptosis via the Hippo pathway

  • Gut Microbes. 2024 Jan-Dec;16(1):2333790. doi: 10.1080/19490976.2024.2333790.
Ni Wang 1 2,  Lu Zhang 1,  Xiao-Xu Leng 1,  Yi-Le Xie 1,  Zi-Ran Kang 1,  Li-Cong Zhao 1,  Lin-Hong Song 1,  Cheng-Bei Zhou 1,  Jing-Yuan Fang 1
Affiliations

Affiliations

  • 1 Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 2 Department of Gastroenterology; Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
PMID: 38533566 DOI: 10.1080/19490976.2024.2333790
Abstract

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal Cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit Pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.

Keywords

Fusobacterium nucleatum; GSDME; YAP; chemoresistance; colorectal cancer; pyroptosis.

Figures
Products