P-124 SHP-2 deficiency in myeloid cells promotes metastasis of esophageal carcinoma via increasing cathepsins and inflammatory factor secretion

Esophageal carcinoma (EC) is one of the most common and aggressive malignancies worldwide, with a high incidence metastasis poor prognosis. The molecular mechanisms underlying EC are still poorly understood. SHP-2 (Src-homology 2 domain-containing phosphatase 2) protein tyrosine that regulates various cellular processes, such as proliferation, differentiation, survival, migration inflammation. has been reported to act either an oncogene or tumor suppressor in different types cancers. However, role remains unclear. authors used mouse model liver by injecting luciferase-labeled cells into spleen SHP-2WT SHP-2MAC-KO mice. They isolated TAMs from tumors flow cytometry analyzed their expression M2-like markers western blot immunofluorescence. also stimulated BMDMs both groups mice IL-10 IL-4 treated them STAT3 STAT6 inhibitors examine effects deficiency cytokine signaling on polarization. We found myeloid-specific knockout (SHP-2MAC-KO) significantly increased number size metastatic cancer nodules compared wild-type (SHP-2WT). observed enhanced activity STAT6, two key transcription factors involved inflammation progression, tumor-associated macrophages (TAMs). Moreover, showed secretion cathepsins B S, proteases degrade extracellular matrix facilitate invasion, well inflammatory IL-6 TNF-α, which promote growth angiogenesis. These were inhibited pharmacological vitro. In summary, we have demonstrated myeloid promotes enhancing STAT3/STAT6 TAMs. Our findings reveal novel suppressive suggest targeting its downstream pathways may be promising strategy for treatment. study provides new insights crosstalk between regulation polarization SHP-2.