[P1-2-53] TGFBI-TAGLN axis regulates cancer stem cell properties in head and neck squamous cell carcinoma
キーワード：TGFBI、partial-EMT、HNSCC
Head and neck squamous cell carcinoma (HNSCC) represents a significant healthcare burden worldwide. Previous study employing single-cell transcriptome analysis identified Transforming growth factor-beta-induced (TGFBI) as a pivotal marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise contribution of TGFBI in HNSCC progression remains unclear. Therefore, we elucidated the role of TGFBI in the malignant behavior of HNSCC cells. By leveraging RNA-sequencing data from the TCGA database, we confirmed that heightened TGFBI expression correlates with an augmented occurrence of lymph node metastasis and unfavorable prognosis among HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhanced sphere forming ability, indicative of stem-cell-like properties. In contrast, TGFBI depletion attenuated sphere formation and suppressed the expression of cancer stem cell (CSC) markers. Through RNA-sequencing analysis conducted on TGFBI-overexpressing and control HNSCC cells, we identified TAGLN (transgelin) as a downstream effector mediating TGFBI-induced sphere formation. Notably, depletion of TAGLN abrogated TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation resulting from TGFBI depletion. Moreover, elevated TAGLN expression exhibited correlations with TGFBI expression, advanced grading, lymph node metastasis, and unfavorable prognosis in HNSCC cases. In conclusion, our findings suggest a potential role for TGFBI in promoting CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and may hold implications for the development of targeted therapies.