hMENA splicing program impacts the clinical outcome of early stage lung cancer patients. How and why?

Background In lung cancer, reliable prognostic indicators of the risk of recurrence are still not available. Alternative splicing represents a potential biomarker of diagnosis, prognosis, invasiveness, and response to therapy in different tumors [1], including lung cancer [2]. Human MENA (hMENA) is an actin regulatory protein that modulates cell adhesion and migration [3]. We have isolated three hMENA splice variants, namely hMENA, hMENA and hMENAΔv6, impacting differently cell shape and function. hMENA expression ensures the integrity of cell-cell adhesion and is associated with an epithelial phenotype, whereas hMENAΔv6 is related to a mesenchymal invasive phenotype. The splicing of hMENA, relevant to epithelial mesenchymal transition, is also regulated by microenvironmental cues [4]. The dynamic reciprocity between tumor and stroma influences the tumor tissue architecture including the T cell localization. This, proposed as a prognostic marker [5], is a prerequisite for antitumor immune surveillance and recently the antibody blockade of immune checkpoints is a new reality in lung cancer treatment [6,7].