The significance of Hippo pathway protein expression in oral squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• The Hippo pathway, comprising MST1/2, LATS1/2, and YAP1, regulates cell proliferation and organ size.
• Dysregulation of the Hippo pathway is implicated in various cancers.
• The role of Hippo pathway proteins in oral squamous cell carcinoma (OSCC) remains largely unexplored.

Purpose of the Study:

• To investigate the expression patterns of major Hippo pathway proteins (MST1/2, LATS1/2, YAP1) in oral epithelial dysplasia (OED), carcinoma in situ (CIS), and OSCC.
• To correlate protein expression with clinicopathological features and tumor progression in OSCC.

Main Methods:

• Immunohistochemical analysis of MST1, MST2, LATS1, LATS2, and YAP1 expression in tissue samples of OED (n=7), CIS (n=14), and OSCC (n=109).
• Correlation of protein expression with tumor differentiation, invasion patterns, epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, vimentin, laminin 5, Slug), and protein arginine methyltransferases (PRMTs).

Main Results:

• Cytoplasmic expression of MST1, LATS1, and LATS2 was generally low across OED, CIS, and OSCC.
• MST2 expression was high in OED, CIS, and poorly differentiated OSCC, but low/lost in differentiated OSCC.
• YAP1 expression was associated with tumor differentiation, being lower in well-differentiated OSCC.
• High MST2 and YAP1 expression correlated with an infiltrative invasion pattern.
• High YAP1 expression was linked to EMT features and high PRMT1/5 expression.

Conclusions:

• MST2 exhibits a distinct expression pattern in differentiated OSCC, suggesting a context-dependent role in tumor progression.
• Elevated YAP1 expression may signify aggressive OSCC with EMT at the invasive front, potentially mediated by PRMTs.