Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential

Abstract

Colorectal cancer (CRC) is presently the second most prevalent global mortality-inducing cancer. CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment. In addition, non-neoplastic cell activities within tumor microenvironments for CRC development have been established. However, interleukin (IL)-33, secreted by such cell types, plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment. IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity (ST)2 receptor. Therefore, how to coordinate tumor microenvironment, design and optimize treatment strategies suitable for CRC, based on IL-33/ST2 signal is a challenge. Even though it has established influences upon immunity-linked conditions, IL-33 effects on CRC progression and prevention and related mechanisms are still controversial. Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention. Moreover, IL-33/ST2 signaling is a potential therapeutic target for CRC.

Keywords: Interleukin 33; Suppressor of tumorigenicity 2 signaling; Tumor microenvironment; Conventional therapies; Colorectal cancer

Core tip: Interleukin (IL)-33 belongs to the IL-1 cytokine family and binds to the suppressor of tumorigenicity (ST)2 receptor. IL-33 plays a key role in cancer progression due to interaction with cellular components in the inflammatory microenvironment of tumors. Therefore, it is a challenge to design and optimize treatment strategies suitable for colorectal cancer (CRC) based on IL-33/ST2 signaling to coordinate the tumor microenvironment. IL-33 also has effects on CRC prevention. These findings implicate multifaceted roles of IL-33 in cancer treatment.