CALIXAR announces the publication of a new article in collaboration with P. SAINTIGNY and J-J DIAZ’s laboratories (Albaret MA et al., 2018, Cancers: Externalized Keratin 8 (eK8): A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells).
The aim of the study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, the authors generated a unique antagonist monoclonal antibody targeting an eight-amino-acid-long domain of eK8, which enabled them to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC).
They showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, the authors demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. They, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations.
CALIXAR contribution to this work was to model the topology of cytokeratin 8 and demonstrate its plasma membrane localization which highlights the added value of our approach for membrane proteins characterization.