Background: Many epidemiological studies suggest an association between cancer and neurodegeneration - two disease processes that seemingly have little in common phenotypically. However, these two diseasesshare dysregulation in certain cellular machineries including cell cycle, cell survival, and cell death, even though the end result is entirely different as uncontrolled cell survival and proliferation is hallmark of cancer while progressive neuronal cell death is hallmark of neurodegeneration. Despite the clinical data connecting these two disease processes, little is known about the molecular links between them. Here we describe CASS4, a novel signaling protein that regulates cellular migration and invasion in cancer cells. CASS4 contains specific binding sites for assembly of larger signaling complexes. We have previously shown that CASS4 directly interacts with FAK to regulate actin cytoskeleton.
Methods/Results: Our structure-function analyses and laboratory based preliminary findings indicate that CASS4 conserve many elements in its structure that prompts this protein to interact with several other proteins implicated in immune function, pathogenesis of developmental disorders, and Alzheimer's disease. Interestingly, CASS4 is found to be part of a common amplicon with the AURKA oncogene, which is often elevated in many cancer types specifically in those that have a higher mutational burden such as non-small cell lung cancer. Our focusedanalysis indicate that CASS4 plays important roles in dysregulation of FAK and MEK/ERK signaling in neuronal cells, an early event during pathogenesis of Alzheimer’s disease.
Conclusion: Our preliminary studyopens up possibility for development of novel therapeutic approaches for Alzheimer’s disease by modulating CASS4-FAK signaling axis.