Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299

Area of Science:

• Cell Biology
• Cancer Research
• Molecular Biology

Background:

• Metastatic cancer cells often lack functional WWOX protein (WWOXd).
• Functional WWOX-expressing (WWOXf) cells exhibit distinct migratory behaviors compared to WWOXd cells.

Purpose of the Study:

• To investigate the mechanisms of interaction between WWOXf and WWOXd cells.
• To explore the role of WWOX protein and its associated signaling pathways in cell-cell recognition and cancer cell behavior.
• To determine if normal cells can be activated to attack metastatic cancer cells.

Main Methods:

• Comparative analysis of WWOXf and WWOXd cell migration and apoptosis.
• Investigation of cell surface epitopes (WWOX286-299 and WWOX7-21) and their role in cell-cell interactions.
• Assessment of the interaction between WWOX and the TGFβ receptor type II (TβRII).
• Evaluation of calcium (Ca2+) influx and cell death responses to UV irradiation.

Main Results:

• WWOXf cells collectively migrate and expel WWOXd cells.
• WWOXd cells induce apoptosis in WWOXf cells via IκBα/ERK/WWOX signaling.
• Specific WWOX epitopes (WWOX286-299 and WWOX7-21) mediate repulsion or attraction between WWOXf and WWOXd cells.
• The WWOX/TβRII complex is crucial for cell recognition; blocking TβRII on WWOXd cells leads to WWOXf-mediated apoptosis.
• WWOXd cells show impaired Ca2+ influx and non-apoptotic explosion, while WWOXf cells exhibit effective Ca2+ influx and bubbling cell death.

Conclusions:

• The WWOX/TβRII complex is essential for cell-cell recognition, maintaining calcium influx efficacy, and controlling cell invasiveness.
• Normal cells can be activated to target and attack metastatic cancer cells.
• Dysfunctional WWOX protein in cancer cells alters their migratory behavior, survival mechanisms, and response to stress.