GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK/STAT signaling pathway, functions in gastric carcinogenesis.

摘要: Dysregulated JAK/STAT signaling has been implicated in the molecular pathogenesis of gastric cancer. However, downstream effectors STAT that facilitate carcinogenesis remain to be explored. We previously identified Drosophila ortholog human GRAMD1B our genome-wide RNAi screen identify novel components pathway Drosophila. Here, we examined involvement JAK/STAT-associated carcinogenesis. found expression is positively regulated by and inhibition decreases STAT3 levels, suggesting existence a positive feedback loop. Consistently, acted synergistically promote cancer cell survival upregulating anti-apoptotic molecule Bcl-xL. Interestingly, immunohistochemical analysis for revealed gradual loss cytoplasmic staining but an increase nuclear accumulation GRAMD1B, as tissue becomes malignant. levels were also significantly associated with clinicopathological features patients, particularly tumor grades lymph node status. Moreover, pSTAT3 (Tyr705) showed correlation tissues, thereby confirming close link between these two molecules vivo. This new knowledge about JAK/STAT-GRAMD1B regulation deepens understanding provides foundation development biomarkers