ID1 in TAMs promoted the progression of non-small-cell carcinoma via increasing NF-κB/NPM1/SHP1/SHP2 signaling induced M2 polarization.

This study aimed to explore the effect of ID1 on promoting the progression of NSCLC (Non-small-cell carcinoma) by mediating the polarization of TAMs toward M2 and its potential mechanisms. NSCLC tumor-associated macrophage models were constructed and divided into groups: NC, ID1-OE, SN50, ID1-OE+SN50, SN50 + NPM1-OE, and ID1-OE+SN50 + NPM1-OE for subsequent experiments. Protein expression was detected by Western blot, IL-4, IL-10, Arginase-1, CD206, Cathepsin-K/L/S levels were measured by Q-PCR, transwell assays were used to assess NSCLC cell migration and invasion, and CCK-8 assays were performed to evaluate NSCLC cell proliferation. And subcutaneous tumor transplantation experiments in nude mice were used to detect the progression of NSCLC. Immunohistochemical staining was used to detect the expression of ID1 and p-NF-κB in human cancerous and adjacent non-cancerous tissues. In tumor-associated macrophages (TAMs), activation of the NF-κB signaling pathway by ID1 leads to NF-κB phosphorylation and increased NPM1 expression. NPM1 in turn amplifies the activity of the NF-κB subunits P50 and P65. These subunits form dimers that enter the nucleus, where they drive the overexpression of SHP1 and SHP2. Once activated, SHP1 and SHP2 push TAMs toward an M2-polarized state. Elevated levels of IL-4, IL-10, arginase-1, CD206, and cathepsin K/L/S are indicative of this change. M2-polarized TAMs increase the ability of non-small cell lung cancer (NSCLC) cells to proliferate, migrate, and invade by secreting these substances. This procedure significantly speeds up tumor development, as demonstrated by in vivo trials. Significantly increased levels of ID1 and phosphorylated NF-κB were found in NSCLC tissues when compared to nearby non-cancerous tissues, according to examinations of clinical samples. All of these findings suggest that this signaling pathway may have pathogenic significance in human non-small cell lung cancer. By boosting NF-κB/NPM1-induced overexpression of SHP1/SHP2 and M2 polarization, ID1 in TAMs accelerates the development of NSCLC.