Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC

TROP2 is an intracellular calcium signal transducer and a prognostic biomarker in many cancers. P16 is a cell cycle gene that negatively regulates cell proliferation and division in most human cancers. Oral squamous cell carcinoma (OSCC) is a common malignant tumor subgroup of head and neck squamous cell carcinoma worldwide. Both CA²⁺-dependent and cell cycle signaling pathways play vital roles in OSCC, although the molecular mechanisms remain to be elucidated. We aimed to examine the function of TROP2 and P16 in regulating intracellular calcium ions and the cell cycle in OSCC cell lines. Furtherly, the mRNA and protein expression levels of TROP2 and P16 in OSCC tissue samples were assessed, and their function was evaluated as potential clinical prognostic biomarkers. TROP2 promoted intracellular calcium ion release in OSCC and induced S phase of the cell cycle. Moreover, Trop2-mediated CA²⁺ inhibited P16 expression through the AMP-activated protein kinase pathway in OSCC. Interestingly, P16 overexpression could not reverse these phenomena in vitro. We also demonstrated that human OSCC tissues showed high TROP2 mRNA and protein expression, and Trop2+/P16- expression is an independent prognostic marker for OSCC patients. Our data suggest that Trop2+/P16- may be a valuable prognostic marker for OSCC and that TROP2 inhibits P16 expression and induces S phase by promoting intracellular calcium release in OSCC.