IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein to transduce multiple signals from the extracellular microenvironment. However, whether IQGAP1 mediates EGF-induced cancer progression has been not observed. In this research, we explored the immunological correlations of IQGAP1. IQGAP1 was up-regulated in most cancer and related to poor prognosis in ovarian cancer. In addition, IQGAP1 was correlated with immune-related genes and tumor-infiltrating lymphocytes. IQGAP1 was a novel EGF-response gene, which was up-regulated by EGF. As the downstream of EGFR, IQGAP1 mediated EGF-induced proliferation, migration and invasion of tumor cells and was essential for EGF-induced PD-L1 expression as well. Mechanically, IQGAP1 interacted with STATs and mediated their phosphorylation. Furthermore, Curcumin inhibited EGFR/IQGAP1 axis to down-regulate PD-L1 and suppress cancer progression. To sum up, IQGAP1 responds to EGF stimulation and mediates EGF-induced phosphorylation of STATs, which is a novel promising target for blocking the EGF-induced cancer progression.
Tianfen Liang,Xinyue Ma,Zhimeng Lv,Yina Shao,Weikang Liang,Chenghua Li
To establish a successful infection, bacteria have evolved highly efficient strategies that enable them to enter host cells and disrupt host transport pathways, thereby creating a favorable intracellular niche for survival. With the occurrence of the phagocytic process, Vibrio cholerae releases the effector VgrG-1 of its type VI secretion system (T6SS), which disrupts the host actin cytoskeleton. It is precisely because of this destruction that a bystander protection effect for extracellular bacterial communities can be established. However, VgrG proteins exist in multiple isoforms. Those lacking additional effector domains are generally considered to function primarily as structural components for T6SS assembly, and their roles in pathogenesis are poorly defined. In this study, we characterized a gene from Vibrio splendidus with a cDNA sequence of 1983 base pairs, designated as the valine-glycine repeat protein G ( VsVgrG ) without actin-crosslinking domain. The expression analysis revealed that both mRNA and protein levels of VsVgrG were significantly enhanced following stimulation with Apostichopus japonicus coelomic fluid. Flow cytometry and bacterial plate count assays demonstrated that VsVgrG knockout significantly reduced V. splendidus internalization. Furthermore, immunofluorescence analysis revealed that, compared to cells treated with the Δ VsVgrG mutant, the actin cytoskeleton of sea cucumber coelomocytes exhibited significant dissociation following infection by the wild-type strain. Mechanistically, we identified A. japonicus IQ Motif Containing GTPase Activating Protein 1 (AjIQGAP1) as a direct host binding partner of VsVgrG. Combined overexpression and inhibitor treatment, we demonstrated that VsVgrG promotes pathogen internalization by targeting AjIQGAP1 via actin-dependent endocytosis pathway. Our findings reveal a potential mechanism for V. splendidus internalization and advance our understanding of universal biological mechanisms in pathogen-host interactions.
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