Influence of transcriptional variants on metastasis.

Cancer metastasis is defined as the dissemination of malignant cells from the primary tumor site, leading to colonization of distant organs and the establishment of a secondary tumor. Metastasis is frequently associated with chemoresistance and is the major cause of cancer-related mortality. Metastatic cells need to acquire the ability to resist to stresses provided by different environments, such as reactive oxygen species, shear stress, hemodynamic forces, stromal composition, and immune responses, to colonize other tissues. Hence, only a small population of cells has a metastasis-initiating potential. Several studies have revealed the misregulation of transcriptional variants during cancer progression, and many splice events can be used to distinguish between normal and tumoral tissue. These variants, which are abnormally expressed in malignant cells, contribute to an adaptive response of tumor cells and the success of the metastatic cascade, promoting an anomalous cell cycle, cellular adhesion, resistance to death, cell survival, migration and invasion. Understanding the different aspects of splicing regulation and the influence of transcriptional variants that control metastatic cells is critical for the development of therapeutic strategies. In this review, we describe how transcriptional variants contribute to metastatic competence and discuss how targeting specific isoforms may be a promising therapeutic strategy.