Core Insights - The research published by Fudan University reveals a novel signaling function of Acetyl-Coenzyme A (AcCoA) in regulating mitophagy through the receptor NLRX1, independent of classical pathways like AMPK and mTOR [3][14][16] - This discovery provides new potential targets and strategies for overcoming resistance to KRAS inhibitors in cancer treatment [3][14][16] Group 1: Mechanism of AcCoA in Mitophagy - AcCoA levels decrease during nutrient deprivation, such as short-term fasting, leading to the activation of mitophagy [5][6] - NLRX1 is identified as a key mediator that directly binds to AcCoA, regulating its signaling role in mitophagy [8][11] Group 2: Experimental Validation - In animal models, fasting resulted in a significant decrease in AcCoA levels in tissues, correlating with increased mitophagy [11] - Supplementing with acetate or knocking out NLRX1 gene can block the fasting-induced mitophagy, indicating the critical role of AcCoA and NLRX1 in this process [11][12] Group 3: Implications for Cancer Treatment - The study indicates that KRAS inhibitors downregulate ACLY expression, reducing AcCoA levels and triggering NLRX1-dependent mitophagy, which may contribute to cancer cell resistance [14] - Short-term fasting may have dual effects in cancer treatment, potentially enhancing immune response while also promoting resistance through mitophagy [14][16] Group 4: Future Directions - Targeting the AcCoA-NLRX1 signaling axis may enhance cancer treatment efficacy and could have implications in various metabolic and neurodegenerative diseases [16]

Core Insights - Tumor-infiltrating bacteria, particularly Fusobacterium nucleatum, are increasingly recognized as key components of the tumor microenvironment (TME) and are linked to cancer recurrence and treatment resistance [2][5] - The recent study published in Cancer Cell highlights a new mechanism by which these bacteria disrupt interactions between cancer epithelial cells and induce cell-cycle arrest, leading to resistance against chemotherapy drug 5-fluorouracil (5-FU) [3][10] Summary by Sections Tumor-Infiltrating Bacteria and Cancer - Tumor-infiltrating bacteria, especially in mucosal sites, are being viewed as critical elements of TME [2] - Specific bacteria have been associated with cancer progression and poor prognosis, such as the enrichment of Fusobacterium nucleatum in colorectal cancer (CRC) tissues [2] Mechanism of Action - The study describes how extracellular bacteria, including Fusobacterium nucleatum, regulate the behavior of cancer epithelial cells [6] - These bacteria are primarily found in the extracellular regions of the TME in colorectal and oral cancers, where cell density, transcriptional activity, and proliferation are reduced [6] Experimental Findings - In vitro experiments show that Fusobacterium nucleatum disrupts epithelial cell contact, causing cells to enter a G0-G1 phase and inhibiting transcriptional activity [6] - This state confers resistance to the chemotherapy drug 5-FU and remodels the tumor microenvironment [6] - The findings were validated through live-cell imaging, spatial analysis, mouse models, and a cohort of 52 colorectal cancer patients [6] Clinical Implications - High loads of Fusobacterium nucleatum in tumors correlate with reduced treatment response [8] - The study emphasizes the potential of targeting microbial-tumor interactions as a therapeutic strategy [10]