<p>Role of GSDMB in Pyroptosis and Cancer</p>

Abstract

Gasdermin B (GSDMB) belongs to the gasdermin (GSDM) family which may adopt different mechanisms of intramolecular domain interactions to modulate their lipidbinding and pore-forming activities. The GSDM family has regulatory functions in cell proliferation and differentiation, especially in pyroptosis process. Pyroptosis is a proinflammatory form of regulated cell death and is designed to attract a nonspecific innate response to the site of infection. For cancer cells, the activation of pyroptosis may promote cell death and exert anticancer properties. Also, recent studies have observed the pyroptosislike features in GSDMB and some researches have shown that GSDMB overexpression occurred in several kinds of cancers; these findings bring a contradiction with the participation of GSDMB in pyroptosis. Although people pay less attention to GSDMB, it still has some essential research value. It is a paradox that GSDMB might participate in programmed cell death, which might put forward a research direction of therapeutic targets for cancer. Here, we review the possible progress of how GSDMB participated in this inflammatory regulation mechanistically and the potential functions of GSDMB in cancer.

RETRACTED: Exosome-Delivered LncHEIH Promotes Gastric Cancer Progression by Upregulating EZH2 and Stimulating Methylation of the GSDME Promoter

“…We analyzed the target genes of EZH2 using Harmonizone website and found 1940 targets from the CHEA Transcription Factor Targets dataset 1 . Then, several well-known tumor suppressor genes related to stem cells in gastric cancer, such as EphB3, E-cadherin, STAT3, P16, PTEN, GSDME, and GSDMB were selected as target genes for the following analysis ( Fujii and Ochiai, 2008 ; Pan et al, 2016 ; Chen et al, 2017 ; Gan et al, 2018 ; Ni et al, 2018 ; Xu et al, 2018 ; Li et al, 2020 ). We determined the expression of these tumor suppressor genes by qRT-PCR when EZH2 was knocked down in lncHEIH-overexpressing cells.…”

USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway

“…Some studies showed that GSDMB can promote pyroptotic death and inhibit the growth of tumor cells 15 . In contrast, in HER2-positive breast cancer patients, the clinical outcome of patients with high expression of GSDMB (about 60% of patients) is signi cantly worse, and the neoadjuvant effect is poor, which is often accompanied by trastuzumab resistance 28,29 .…”

TCGA data mining suggested that high GSDMB expression in bladder cancer indicated an excellent prognosis

“…Most current bladder etiology studies focus on genetic changes [12]. Oncogenes are mutated forms of proto-oncogenes that encode growth factors and receptor proteins necessary for normal cell growth [1]. Mutations in protooncogenes can lead to uncontrolled cell division and bladder cancer recurrence and progression.…”

“…GasderminB(GSDMB) is a member of the Gasdermin(GSDM) family and can be regulated by different intramolecular domain interaction mechanisms for lipid binding and pore forming activity [1]. According to previous studies on human cancers, GSDMB is highly expressed not only in healthy tissues (such as lymphocytes, esophagus, stomach, liver, colon, skin epithelium and gastrointestinal tract), but also in gastric cancer, uterine cancer, cervical cancer, breast cancer and other cancer tissues [2,3].…”