S100A4 influences cancer stem cell-like properties of MGC803 gastric cancer cells by regulating GDF15 expression

Abstract

Many studies have revealed that S100A4 is involved in cancer progression by affecting a variety of biological functions. Our previous study showed that S100A4 influences many biological properties of gastric cancer cells; however, the underlying mechanisms are far from clear. In this study, we used cDNA microarray analysis to investigate the global alterations in gene expression in MGC803 gastric cancer cells after siRNA-mediated S100A4 inhibition. Among the total genes investigated, 179 differentially expressed genes (38 upregulated and 141 downregulated) were detected in S100A4-siRNA transfected MGC803 cells compared with NC-siRNA transfected cells. We focused on the GDF15 gene, which was significantly downregulated after S100A4 inhibition. ChIP studies showed that the S100A4 protein binds to the GDF15 promoter, implicating S100A4 in GDF15 regulation at the transcriptional level. GDF15 overexpression promoted CSC-like properties of MGC803 cells, such as spheroid and soft-agar colony forming abilities. S100A4 inhibition suppressed the CSC-like properties of the cells, whereas, GV141-GDF15 vector transfection reversed these effects. Our results suggest that S100A4 influences the CSC-like properties of MGC803 gastric cancer cells by regulating GDF15 expression.

FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells

“…But the mechanisms underlying the decreased expression of FAM107B in cancers are not clear. Based on our previous findings from cDNA microarray that there are 179 differentially expressed genes after S100A4 inhibition in gastric cancer cells MGC803 (Guo et al, 2016), FAM107B was an upregulated one among them, but it was not shown and verified then. In the present study, we confirmed that FAM107B expression was upregulated in MGC803 cells after S100A4 inhibition by qRT-PCR and Western blot.…”

“…The increased S100A4 expression was closely correlated with invasion, lymph node metastasis, and poor prognosis of gastric cancer (Li et al, 2013;Natarajan et al, 2014;Niu et al, 2015). Recently, we analyzed the differentially expressed gene profile after S100A4 inhibition in gastric cancer cells MGC803 by cDNA microarray and identified 179 differentially expressed genes (Guo et al, 2016). Among them, FAM107B was an upregulated gene after S100A4 inhibition in the cells, which was not shown then and needed to be confirmed.…”

“…By screening a multiple organ tumor and normal tissue microarray, Nakajima et al (2012) found that HITS expression was decreased in tumor tissues of the stomach, breast, thyroid, and other kinds of tissues. Recently, we analyzed the differentially expressed gene profile after S100A4 inhibition in gastric cancer cells MGC803 by cDNA microarray and identified 179 differentially expressed genes (Guo et al, 2016). It was supposed that FAM107B may function as a tumor suppressor gene and its abnormalities may be involved in the progression of cancers.…”

S100A4 in cancer progression and metastasis: A systematic review

“…S100A4 oxidation could be induced by hydrogen peroxide treatment in gastric cancer cells, decreasing S100A4-PP5 interaction and the inhibition of PP5 activation process, which is closely associated with gastric cancer cell malignant phenotypes [ 90 ]. S100A4 can also promote the cancer stem cell (CSC)-like properties in gastric cancer cells by the enhancement of growth differentiation factor 15 (GDF15) expression, i.e., S100A4 binds to the GDF15 promoter to induce CSC-like properties in gastric cancer cells, including the formation of spheroid and soft-agar colonies [ 91 ]. Recently, a noninvasive and reliable method was developed to quantitatively determine levels of S100A4 transcripts in human blood plasma that allowed for early-defining of cancer-staging and risk for metastasis of gastric cancer, which contributed to initial and additional individual therapy for improving survival of gastric cancer patients [ 92 ].…”

miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2

“…Our previous studies showed that S100A4 suppression by RNA interference (RNAi) could inhibit the proliferation and migration of GC cells, and promote their anoikis [ 7 , 8 , 9 ]. To investigate the underlying mechanism by which S100A4 affects the properties of GC cells, we analyzed the differentially expressed gene profile using a cDNA microarray after S100A4 suppression in GC cell line MGC803, and found that GDF15 was significantly downregulated among the 173 differentially expressed genes, and could mediate the effect of S100A4 on the properties of GC cells [ 10 ].…”