Abstract 5943: The role of IL-6 family cytokines in gastrointestinal cancer

Abstract

Abstract The important effector of the Hippo pathway, YAP, is strongly activated in the majority of gastrointestinal cancer. However, the mechanism by which YAP is activated in gastrointestinal cancer remains unknown. Previously, we found that after intestinal injury, IL-6 family cytokines activate the Src family kinases (SFK)-YAP pathway, which enhances intestinal regeneration. Here, we found that in addition to β-catenin, loss of tumor suppressor adenomatous polyposis coli (APC) activates SFKs, YAP and STAT3, which are simultaneously activated in 60-70% of human colorectal cancer specimens. We also found that up-regulation of IL-6 signal transducer (IL-6ST/gp130), which is induced by YAP activation, causes the activation of SFKs, YAP and STAT3. We also found that leukemia inhibitory factor (LIF), one of the IL-6 family cytokines, plays an important role in human esophageal squamous cell carcinoma by activating the SFK-YAP pathway. The combination treatment of SFK and JAK inhibitors results in suppression of gastrointestinal tumors. These results suggest that these signaling pathways might be new attractive therapeutic targets in human gastrointestinal cancer. Citation Format: Koji Taniguchi, Tetsuro Kawazoe. The role of IL-6 family cytokines in gastrointestinal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5943.