2. Academic Validation
  3. Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation

Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation

  • PLoS Pathog. 2023 Feb 22;19(2):e1011189. doi: 10.1371/journal.ppat.1011189.
Dan-Ni Wang 1,  Jin-Jing Ni 1,  Jian-Hui Li 1 2,  Ya-Qi Gao 3,  Fang-Jing Ni 1,  Zhen-Zhen Zhang 4,  Jing-Yuan Fang 3,  Jie Lu 5,  Yu-Feng Yao 1 5 6 7
Affiliations

Affiliations

  • 1 Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • 3 State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • 7 Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China.
PMID: 36812247 DOI: 10.1371/journal.ppat.1011189
Abstract

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella Infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in Cancer cells, is drastically reduced after Bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell Apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon Cancer cells. The low level of K153 acetylation in patients with colorectal Cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of Bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

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