HHEX suppresses advanced thyroid cancer by interacting with TLE3

Area of Science:

• Endocrinology
• Molecular Biology
• Oncology

Background:

• The Haematopoietically Expressed Homeobox (HHEX) gene is crucial for thyroid gland development and differentiation.
• HHEX is often downregulated in thyroid cancer, but its precise role and mechanisms are not fully understood.

Purpose of the Study:

• To investigate the function of HHEX in thyroid cancer.
• To elucidate the molecular mechanisms underlying HHEX's role in thyroid tumorigenesis and differentiation.

Main Methods:

• Analysis of HHEX expression and localization in thyroid cancer cell lines.
• In vitro and in vivo experiments involving HHEX knockdown and overexpression.
• Assessment of cell proliferation, migration, invasion, and sodium iodine symporter (NIS) activity.
• Investigation of HHEX's interaction with the TLE3 protein and the Wnt/β-catenin signaling pathway.

Main Results:

• HHEX was found to be downregulated and aberrantly localized in cytoplasm in thyroid cancer cells.
• HHEX knockdown promoted, while overexpression inhibited, cancer cell proliferation, migration, and invasion.
• Overexpression of HHEX upregulated NIS expression and promoter activity, indicating enhanced thyroid differentiation.
• HHEX regulates TLE3 protein levels, inhibiting Wnt/β-catenin signaling by preventing TLE3 cytoplasmic translocation and ubiquitination.

Conclusions:

• HHEX functions as a tumor suppressor in thyroid cancer.
• Restoring HHEX expression can inhibit tumor progression and promote differentiation.
• Targeting HHEX represents a potential therapeutic strategy for advanced thyroid cancer.