Inhibition of THBS1 axis contributes to the antitumor effect of PA-MSHA in anaplastic thyroid cancer.

Abstract

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, has the worst prognosis, and lacks effective treatment in clinical practice. Thrombospondin-1 (THBS1) is a multifunctional extracellular matrix (ECM) glycoprotein that regulates cell proliferation, apoptosis, and metastasis, and is considered a potential clinical biomarker for the monitoring and prognostication of various tumors. However, the specific roles and molecular mechanisms of action of THBS1 in ATC remain unclear. In this study, we found that Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a THBS1 inhibitor, significantly inhibited ATC tumor growth both in vitro and in vivo. Mechanistically, we demonstrated that THBS1 was the target gene of PA-MSHA in ATC and identified the THBS1/FAK/AKT axis as the key antitumor signaling pathway. Furthermore, we confirmed that THBS1 was overexpressed in ATC tumors and that high levels of THBS1 were associated with a poorer prognosis in thyroid cancer. Silencing THBS1 significantly decreased p-FAK and p-AKT levels, resulting in significant inhibition of cell proliferation and apoptosis in ATC cells. These findings suggest that the THBS1/FAK/AKT axis is a promising therapeutic target for ATC treatment.