YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing...

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• The Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) pathway is recognized as a key driver in various cancers.
• The specific role and underlying mechanisms of the YAP/TAZ-TEAD pathway in the development of cervical intraepithelial neoplasia (CIN) remain largely unelucidated.

Purpose of the Study:

• To investigate the effect of YAP/TAZ-TEAD pathway activity on the development of CIN.
• To explore potential new strategies for the diagnosis and treatment of CIN based on this pathway.

Main Methods:

• Cervical tissues from CIN patients (CIN1, CIN2/3, SCC) and healthy controls were analyzed for YAP, TAZ, and TEAD expression using immunohistochemistry, qRT-PCR, and western blot.
• Cell lines (Z172, Z183) were manipulated via siRNA-mediated knockdown of YAP/TAZ and TEAD, or overexpression of YAP/TAZ (YAP-5SA).
• Cellular stemness, glycolysis, and malignant transformation were assessed using sphere formation assays, commercial kits, MTT, Transwell, scratch assays, and xenotransplantation.

Main Results:

• YAP, TAZ, and TEAD expression significantly increased in CIN2/3 and SCC tissues and cell lines compared to normal tissues.
• Knockdown of YAP/TAZ inhibited stemness, glycolysis, and malignant transformation, while YAP/TAZ activation promoted these characteristics.
• Simultaneous activation of YAP/TAZ and knockdown of TEAD attenuated the pro-malignant effects of YAP/TAZ activation.

Conclusions:

• The YAP/TAZ-TEAD signaling pathway is upregulated in CIN progression and promotes malignant transformation.
• This pathway enhances cancer stem cell characteristics and the Warburg effect, contributing to CIN development.
• Targeting the YAP/TAZ-TEAD pathway presents a promising avenue for CIN diagnosis and therapeutic intervention.