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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Anaplastic thyroid cancer (ATC) is highly aggressive with limited treatment options.
• Thrombospondin-1 (THBS1), an extracellular matrix protein, influences tumor progression but its role in ATC is unclear.
• THBS1 is a potential biomarker for various cancers.

Purpose of the Study:

• To investigate the role and molecular mechanisms of THBS1 in anaplastic thyroid cancer.
• To identify potential therapeutic targets for ATC treatment.

Main Methods:

• Utilized Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) as a THBS1 inhibitor.
• Assessed tumor growth inhibition in vitro and in vivo.
• Investigated the THBS1/FAK/AKT signaling pathway.
• Analyzed THBS1 expression in ATC tumors and correlated it with patient prognosis.
• Performed THBS1 gene silencing experiments.

Main Results:

• PA-MSHA significantly inhibited ATC tumor growth.
• THBS1 was identified as the target of PA-MSHA in ATC.
• The THBS1/FAK/AKT axis was identified as a key pathway in ATC.
• THBS1 was overexpressed in ATC, correlating with poor prognosis.
• THBS1 silencing reduced proliferation and increased apoptosis in ATC cells by downregulating p-FAK and p-AKT.

Conclusions:

• The THBS1/FAK/AKT axis plays a critical role in anaplastic thyroid cancer progression.
• Targeting THBS1 presents a potential therapeutic strategy for ATC.
• PA-MSHA demonstrates antitumor effects in ATC by inhibiting THBS1.