LATS1 inhibits metastasis and epithelial-mesenchymal transition in head and neck squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• The Hippo signaling pathway regulates organ size and tumor suppression.
• Large tumor suppressor kinase 1 (LATS1) is a key component of the Hippo pathway, known to inactivate YAP1 and WWTR1.
• Understanding LATS1's role in head and neck squamous cell carcinomas (HNSCCs) is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the functional roles of LATS1 expression in HNSCC.
• To analyze LATS1 expression patterns in HNSCC tissues and correlate them with clinical features.
• To explore the potential of LATS1 as a therapeutic target for HNSCC.

Main Methods:

• LATS1-expressing plasmid transfection into B88 cells to assess phenotypic changes.
• Immunohistochemistry on tissue microarrays, Oncomine, and TCGA databases for LATS1 expression analysis.
• Western blot analysis to detect specific protein markers (Twist, N-cadherin).
• Bioinformatic analysis and Cox proportional hazards modeling for survival analysis.

Main Results:

• LATS1 overexpression suppressed HNSCC cell growth, migration, and invasion, while inducing apoptosis and G2 arrest.
• Increased expression of P21, Bax, and E-cadherin, and decreased expression of Cyclin B1, D1, Bcl-2, and MMPs were observed with LATS1 overexpression.
• Nuclear LATS1 expression was lower in primary HNSCC than normal tissue, while cytoplasmic expression was higher and correlated with lymph node metastasis.
• Upregulated LATS1 mRNA expression was found in HNSCCs, and differentiation degree, perineural invasion, and distant metastasis were independent prognostic factors.

Conclusions:

• LATS1 exhibits tumor-suppressive functions in HNSCC, inhibiting aggressive phenotypes.
• Nucleocytoplasmic translocation of LATS1 protein and upregulated LATS1 mRNA occur during HNSCC tumorigenesis.
• LATS1 mRNA overexpression holds promise as a potential gene therapy target for HNSCC, aiming to reverse aggressive cellular behaviors.