Expression of GSDML Associates with Tumor Progression in Uterine Cervix Cancer

Abstract

Gasdermin-like (GSDML) belongs to the gasdermin-domain-containing protein family (GSDMDC family) that is involved in carcinogenesis and hearing impairment. However, the role of GSDML in carcinogenesis remains unclear. In this study, we identified four isoforms of GSDML gene. The primary and longest isoform GSDML1 is widely expressed in human cancer cell lines. GFP-GSDML1 fusion protein was localized predominantly in the nucleus of human breast cancer MCF7 and cervical cancer HeLa cells but exclusively in the cytoplasm of hepatocellular carcinoma HepG2 cells. Importantly, immunohistochemistry analysis showed that the GSDML protein in the nuclei is expressed at a higher level in uterine cervix cancer tissues than in the adjacent cancer tissues and corresponding nonneoplastic tissues. Such significance was not observed in hepatocellular carcinoma tissues. Ectopic expression of GSDML1 enhanced the growth of cultured cells, whereas inhibition of its endogenous expression decreased proliferation. Furthermore, GSDML1 had significant effects on promoting bromodeoxyuridine incorporation in cells. However, GSDML1 could neither promote malignant transformation nor gain the ability of colony formation or carcinogenicity on nude mice. Collectively, these results suggest that GSDML can promote cell proliferation, and it might be correlated with carcinogenesis and progression of uterine cervix cancer.

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein

“…consistent with the cell proliferation activity observed for GSDMB (7). Contrarily, Ding et al showed that the N-terminal domain of GSDMB does induce pyroptosis of HEK293T cells (25).…”

“…Currently, the subcellular location of GSDMB is not welldefined because it was localized primarily in the nucleolus of human epithelial breast (MCF7) and cervical cancer (HeLa) cells (7), or exclusively in the cytoplasm of MCF7 breast cancer cells (8). Human GSDMB has six splice isoforms (Q8TAX9; UniProt Knowledge Base).…”

“…The mouse genome contains three clusters of GSDM genes, encoding eight GSDMs (Gsdma1 to -3, Gsdmc1 to -4, and Gsdmd), but lacks the analog of the human GSDMB (also known as GSDML or PRO2521) (1). Based on the differential protein expressions in gastric and esophageal cancers, human GSDMA, GSDMC, and GSDMD are considered tumor suppressors whereas an overexpression of GSDMB in gastric, uterine cervix, and breast cancers was accompanied by tumor progression and metastasis (3)(4)(5)(6)(7)(8). The overexpression of GSDMC in metastatic melanoma cells is an exception to its apoptotic role (9).…”

Alu-derived cis-element regulates tumorigenesis-dependent gastric expression of GASDERMIN B (GSDMB)

“…It was reported that forced expression of full-length GSDMB could neither promote malignant transformation of CHO cells nor confer colony formation ability or carcinogenicity to CHO cells in nude mice (Sun et al, 2008). These findings suggest that over-expression and ectopic expression of the full-length GSDMB transcript has no effect on cancer development and progression.…”

“…Moreover, it was recently reported that GSDMA is involved in the TGF-beta signaling that mediates apoptosis in the gastric epithelium (Saeki et al, 2007). In contrast, GSDMB is expressed in human cancer tissues, including gastric, hepatic, colon, uterine, and cervical cancers, and cancer-derived cell lines (Carl-McGrath et al, 2008;Sun et al, 2008). Although GSDMA and GSDMB belong to the same gene family and are located near to each other on 17q21, expression of GSDMA and GSDMB during cancer development and progression are non-overlapping and complementary.…”