Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation

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.

Uncovering the Importance of Ligand Mobility on Cellular Uptake of Nanoparticles: Insights from Experimental, Computational, and Theoretical Investigations

“…In addition to conventional endocytosis, there exist other noncanonical pathways through which cell can leverage to internalize nanomaterials independent of clathrin and caveolin. , Two representative pathways, namely, the clathrin-independent carriers-glycosylphosphotidylinositol-anchored protein enriched compartments (CLIC-GEEC) and fast endophilin-mediated endocytosis (FEME), have been identified and may play crucial roles in the uptake of nanoparticles. We first investigated the distribution profiles of key regulators in CLIC-GEEC and FEME processes, namely, Cdc42, Arf6, and endophilin, respectively.…”

“…As such, actin network can assemble at the cell cortex, serving a critical role in cellular uptake of substances through CLIC-GEEC. Wang et al reported 41 that the subcellular traffic of Cdc42 to cell cortex is crucial for its role as a cytoskeleton modulator. Our results further prove that fine-tuning of ligand mobility, without changing the nanoparticles of choice, holds the promise of conveniently inducing Cdc42-mediated CLIC-GEEC.…”

Ceramide-1-phosphate is a regulator of Golgi structure and is co-opted by the obligate intracellular bacterial pathogen Anaplasma phagocytophilum

“…PKCα is an upstream regulator of JNK and promotes its recruitment to cellular membranes ( 94 – 102 ). Cdc42 is also as an upstream activator of JNK ( 11 , 103 – 106 ). PKCα and JNK regulate phosphorylation of GRASP55 and GRASP65, respectively ( 19 , 68 ).…”

MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats

“…The copyright holder for this preprint this version posted March 22, 2024. ; https://doi.org/10.1101/2024.03.21.586086 doi: bioRxiv preprint processes, including cell division, intracellular transport, gene transcription, cell cycle regulation, and regulates cell growth and stability. [29][30][31] We overexpressed miR-206 within VEGFA-treated BM-MSCs to detect the expression levels of CDC42 gene and protein in the cells. It was found that the expression of CDC42 was down-regulated in cells transfected with miR-206.…”