Downregulation of gasdermin D promotes gastric cancer
proliferation by regulating cell cycle-related proteins
Wei Jie WANG,* Di CHEN,* Ming Zuo JIANG,* Bing XU,* Xiao Wei LI,* Yi CHU,* Yu Jie ZHANG,*
Jie LIANG ,* & Dai Ming FAN*
*State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Air Force Military
Medical University, Xi’an, Shaanxi Province, and
Department of Gastroenterology, First Afﬁliated Hospital of
Sun Yat-Sen University, Guangzhou, Guangdong Province, China
OBJECTIVE: To explore the relationship between
gasdermin D (GSDMD) and gastric cancer (GC) cell
proliferation, and to determine whether the downre-
gulated expression of GSDMD contributed to the
tumorigenesis and proliferation of GC cells.
METHODS: GSDMD expressions in GC tissues and
matched adjacent non-cancerous tissues were
assessed by quantitative real-time polymerase chain
reaction, Western blot and immunohistochemistry.
The effect of GSDMD on cell proliferation in vitro
was assessed by the colony formation assay and cell
viability assays. In vivo, xenografted tumors in nude
mice were evaluated. The cell cycle was analyzed by
ﬂow cytometry. In addition, the alterations of several
cell cycle-related and cell signaling pathway proteins
were analyzed by Western blot.
RESULTS: GSDMD expression was decreased in GC,
and the decreased expression of GSDMD could mark-
edly promote the proliferation of tumors in vivo and
in vitro. The downregulation of GSDMD accelerated
cell transition by activating extracellular signal reg-
ulated kinase, signal transducer and activator of tran-
scription 3 and phosphatidylinositol 3 kinase/protein
kinase B signaling pathways and regulating cell cycle-
related proteins in GC.
CONCLUSION: GSDMD may protect against cell
proliferation of GC, and it may be used as a diagnos-
tic and treatment strategy for GC.
KEY WORDS: cell cycle, cell proliferation, human GSDMD protein, mouse GSDMD protein, pyroptosis,
Gastric cancer (GC) is the fourth most common
cancer in man and the ﬁfth most common cancer
in women worldwide, with a high mortality.
is a multifactorial disorder that results from
abnormal activation of several oncogenic signaling
pathways, the activation of oncogenes, the inacti-
vation of tumor suppressor genes and the dysregu-
lation of cell cycle-related proteins.
molecular mechanism underlying GC remains
Correspondence to: Jie LIANG, State Key Laboratory of Cancer Biology
and Xijing Hospital of Digestive Diseases, Air Force Military Medical
University, 17 West Changle Road, Xi’an, Shaanxi Province 710032,
China. Email: firstname.lastname@example.org; Dai Ming FAN, State Key
Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases,
Air Force Military Medical University, 17 West Changle Road, Xi’an,
Shaanxi Province 710032, China. Email: email@example.com
Conﬂict of interest: None.
Accepted for publication 29 December 2017.
© 2018 Chinese Medical Association Shanghai Branch, Chinese
Society of Gastroenterology, Renji Hospital Afﬁliated to Shanghai
Jiaotong University School of Medicine and John Wiley & Sons
Journal of Digestive Diseases 2018; 19; 74–83 doi: 10.1111/1751-2980.12576