![]() ![]() Consistently, in large series of breast cancer samples GSDMB2 expression, and not of exon6-containing variants (GSDMB3-4), associates with unfavourable clinical-pathological parameters. Here, we first prove that exon 6 translation (in the interdomain protein linker) is essential for pyroptosis, and therefore, GSDMB isoforms lacking this exon (GSDMB1-2) cannot provoke cancer cell death. However, it is still unknown the precise regulatory mechanisms of GSDMB pyroptosis as well as the differential effects of the four translated GSDMB variants (GSDMB1-4, that differ in the alternative usage of exons 6-7) in this process. GSDMB is promising oncologic therapeutic target since it exhibits either antitumor function, when immunocyte-mediated Granzyme-A (GZMA) cleaves GSDMB releasing its cytotoxic N-terminal domain, or pro-tumoral activities (invasion, metastasis, and drug resistance). Gasdermin-B (GSDMB) plays complex and controversial roles in pathologies, with pyroptosis-dependent and independent functions. ![]() The formation of Gasdermin (GSDM) pores, leading to pyroptosis or other context-dependent consequences, is directly involved in multiple diseases. ![]()
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