Thrombospondin‑1 triggers calreticulin expression in human mucoepidermoid carcinoma MC‑3 cells via the PERK/CHOP pathway

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, accounting for ~30% of all salivary gland malignancies; however, effective treatments for advanced‑stage disease remain limited. The induction of immunogenic cell death (ICD) has emerged as a potent anti‑tumor intervention for MEC. Thrombospondin‑1 (TSP‑1) exhibits documented anti‑tumor properties in MEC; however, its capacity to drive ICD‑mediated tumor suppression remains poorly understood. In the present study, the mechanistic role of TSP‑1 was investigated in MC‑3 cells across four experimental cohorts: Control, TSP‑1, TSP‑1 combined with a PERK inhibitor (ISRIB) and TSP‑1 combined with a PERK activator (CCT020312). Cellular assays, including flow cytometry, immunofluorescence and western blot analysis, revealed that TSP‑1 triggered ICD at 72 h, characterized by a significant increase in calreticulin (CRT) surface exposure. Mechanistically, pharmacological inhibition of PERK attenuated the expression of the PERK/CHOP axis. Notably, while the 4 h TSP‑1 monotherapy showed negligible effects on CRT, the integration of the PERK inhibitor markedly diminished PERK/CHOP/CRT signaling. Collectively, the present data indicated that TSP‑1 facilitated ICD and CRT translocation in MEC cells via the activation of the PERK/CHOP signaling cascade. These results provide a rationale for further in vivo investigations to substantiate the therapeutic potential of TSP‑1‑induced ICD in MEC management.