Publications
EPHA2-Ephrin-B1 cis-interaction drives an oncogenic reverse signaling, leading to the recurrence of oral cancer
Reshma Raj R, Nandini Datta, Soumya Krishnan U, Geetha Shanmugam, Jiss Maria Louis, Ravichandran Damodaran Jeyaram, Keshava K. Datta, Harsha Gowda, Meghna Sarkar, Madhumathy G. Nair, Jyothy S. Prabhu, Hafsa Shabeer, Balagopal P. G, Thameem A, Alan Jose, Vishnu Sunil Jaikumar & Tessy Thomas Maliekal This collaborative study identified a novel cis-interaction between EPHA2 and Ephrin-B1 in self-renewing oral cancer cells. EPHA2 directly phosphorylated Ephrin-B1 at Y317 and Y324/329, thereby activating JNK-mediated reverse signaling. Disruption of EPHA2 expression or Ephrin-B1 phosphorylation reduced cancer stem-cell frequency and tumour-initiating capacity. The FNIII domain of EPHA2 was essential for this interaction, while high co-expression of EPHA2 and Ephrin-B1 was associated with recurrence and poor patient survival. These findings establish Ephrin-B1 as an oncogenic ligand and highlight EPHA2–Ephrin-B1 cis-signaling as a potential therapeutic target in recurrent oral cancer.