Extrajunctional CLDN10 cooperates with LAT1 and accelerates clear cell renal cell carcinoma progression

Area of Science:

• Cellular biology
• Molecular oncology
• Cancer signaling

Background:

• Claudins (CLDNs) are cell adhesion molecules with signaling capabilities influencing cancer progression.
• The precise mechanisms of CLDN-adhesion signaling in cancer remain incompletely understood.
• This study investigates the role of CLDN10 in clear cell renal cell carcinoma (ccRCC) signaling and malignancy.

Purpose of the Study:

• To determine if CLDN10 promotes intracellular signals and malignant phenotypes in ccRCC.
• To identify CLDN10-interacting proteins and elucidate their functional significance.
• To establish CLDN10 as a potential prognostic marker in ccRCC.

Main Methods:

• Development of a novel monoclonal antibody for CLDN10 detection.
• Immunohistochemistry on 165 ccRCC patient samples to assess clinicopathological significance.
• Generation of ccRCC cell lines with varying CLDN10 expression for phenotypic analysis.
• Immunoprecipitation-mass spectrometry to identify CLDN10-interacting proteins, including LAT1.

Main Results:

• High CLDN10 expression is a significant predictor of poor outcome and an independent prognostic marker for cancer-specific survival in ccRCC.
• CLDN10 expression enhances ccRCC cell viability, proliferation, migration, and tumor growth.
• CLDN10 activates mTOR signaling and downstream targets, forming a complex with LAT1 to facilitate malignant phenotypes.
• Evidence suggests interaction between CLDN10-TM1 and LAT1-TM4.

Conclusions:

• CLDN10-LAT1 signaling is a key driver of ccRCC progression.
• CLDNs mediate distinct intracellular signals based on their binding partners, such as LAT1 and Src-family kinases.
• CLDN10 represents a novel therapeutic target and prognostic biomarker for ccRCC.