Targeting SHP2: Dual breakthroughs in colorectal cancer therapy–from signaling pathway modulation to immune microenvironment remodeling

Figure 2 SHP2 regulates the STAT3 pathway. SHP2 negatively regulates STAT3 in colorectal cancer, correlating with improved disease-specific survival and disease-free survival. TRIM52 deletion suppresses STAT3 phosphorylation via SHP2 upregulation, inhibiting tumor growth. SHP2 dephosphorylates STAT3 to block proliferation, while mutant p53 competitively binds to STAT3 to reverse this suppression. Paradoxically, the SHP2-IL22R1 interaction activates STAT3-mediated JAK/STAT signaling, driving proliferation. Created with biogdp.com (Supplementary material).