Activation of tumor suppressor LKB1 abrogates growth and cancer stem-like phenotype of oral carcinoma via inhibition of oncogenic Stat3

Background Oral carcinoma is a prevalent malignancy with limited therapeutic options, highlighting the need to elucidate molecular mechanisms driving tumor progression. Aim This study explores the interplay between LKB1 and STAT3 signaling pathways in Oral carcinoma pathogenesis. Methods Two Oral carcinoma cell lines including HSC-3 and KB were used. Results We demonstrate that honokiol, an LKB1 activator, unexpectedly enhances the growth of oral carcinoma cells, while genetic knockdown of LKB1 further promotes cell proliferation, suggesting a context-dependent tumor-suppressive role for LKB1 in Oral carcinoma. Mechanistically, honokiol inhibits phosphorylation of STAT3 (p-STAT3), a key oncogenic driver, in oral carcinoma cells. Consistent with this, pharmacological inhibition of p-STAT3 using Stattic suppresses Oral carcinoma cell growth, whereas activation of STAT3 with Colivelin promotes proliferation, underscoring the critical role of STAT3 signaling in Oral carcinoma progression. Importantly, Colivelin rescues honokiol-mediated growth inhibition, indicating that honokiol exerts its antitumor effects, at least in part, through suppression of STAT3 activity. These findings reveal a novel crosstalk between LKB1 and STAT3 pathways in oral carcinoma and suggest that targeting STAT3 signaling may represent a promising therapeutic strategy for oral cancer. Conclusion This study provides new insights into the molecular mechanisms underlying oral carcinoma progression and identifies potential targets for therapeutic intervention.