IFNγ synergies with cold atmospheric plasma in triggering colorectal cancer cell ferroptosis via the IFNγ/IFNR2/APC/TCF4/GPX4 axis.

Colorectal cancer accounts for the second most common cancer-related lethality. Intestinal stem cells are responsible for enteric homeostasis maintenance that, once being transformed, become colorectal cancer stem cells. Arresting cancer stemness represents an innovative strategy for colorectal cancer management. Using intestinal stem cell organoids as the primary model, we screened common inflammatory cytokines to identify key players targeting cancer stemness. We also explored the downstream signaling that drives the functionalities of the identified cytokine through both experimental investigations and computational predictions. As the results, we identified IFNγ as the key cytokine capable of arresting intestinal stem cells via the IFNγ/IFNGR2/APC/TCF4/GPX4 axis, proposed its role in killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis, and demonstrated its synergistic anti-cancer effect with cold atmospheric plasma in killing colorectal cancer cells that is worthy to be experimentally validated.

Expression profiling based on graph-clustering approach to determine colon cancer pathway.

CONTEXT: Colorectal cancer is the second leading cause of cancer deaths worldwide. DNA microarray-based technologies allow simultaneous analysis of expression of thousands of genes. AIM: To search for important molecular markers and pathways that hold great promise for further treatment of patients with colorectal cancer. MATERIALS AND METHODS: Here, we performed a comprehensive gene-level assessment of colorectal cancer using 35 colorectal cancer and 24 normal samples. RESULTS: It was shown that AURKA, MT1G, and AKAP12 had a high degree of response in colorectal cancer. Besides, we further explored the underlying molecular mechanism within these different genes. CONCLUSIONS: The results indicated calcium signaling pathway and vascular smooth muscle contraction pathway were the two significant pathways, giving hope to provide insights into the development of novel therapeutic targets and pathways.