KAT5 promotes invasion and metastasis through C-MYC stabilization in ATC

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Anaplastic thyroid cancer (ATC) is highly aggressive with a poor prognosis, and its underlying mechanisms remain unclear.
• Components of the DNA damage response (DDR) are often altered in ATC, suggesting their involvement in cancer progression.

Purpose of the Study:

• To investigate the functional role of histone acetyltransferase KAT5, a key DDR protein, in promoting ATC invasiveness and metastasis.
• To establish a link between KAT5 expression, C-MYC stabilization, and the aggressive phenotype of ATC.

Main Methods:

• Immunohistochemical analysis of KAT5 expression in 82 ATC patient samples, correlating with metastasis and survival.
• In vitro studies using cellular models to assess the impact of KAT5 modulation on cancer cell proliferation and invasion.
• In vivo experiments in nude mice to evaluate the effect of altered KAT5 expression on ATC metastasis.

Main Results:

• KAT5 expression strongly correlates with metastasis and reduced overall survival in ATC patients (P = 0.0009 and P = 0.0017, respectively).
• Upregulation of KAT5 significantly enhances thyroid cancer cell proliferation and invasion in vitro.
• KAT5 stabilizes C-MYC by inhibiting its degradation and direct acetylation, thereby promoting ATC invasion and metastasis in vivo.

Conclusions:

• KAT5 promotes ATC invasion and metastasis through the stabilization of C-MYC.
• KAT5 represents a novel biomarker and a potential therapeutic target for anaplastic thyroid cancer.