S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

Li, Fengping; Shi, Jiaolong; Xu, Zhijun; Yao, Xiang; Mou, Tingyu; Yu, Jiang; Liu, Hao; Li, Guoxin

doi:10.7150/jca.25469

Cited by 43 publications

(31 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, MYH9 overexpression was induced by LIM kinase 1 (LIMK1) and promoted growth and metastasis by activating MAPK/AKT signaling in colorectal cancer 33,34 . The S100A4‐MYH9 axis could promote migration and invasion through inducing transforming growth factor‐β‐mediated epithelial‐mesenchymal transition in gastric cancer 35 . In addition, MYH9 was downregulated by miR‐124, miR‐647, or let‐7f to suppress invasion and metastasis in colorectal or gastric cancer 36‐38 .…”

Section: Discussionmentioning

confidence: 99%

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Yang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.

show abstract

Section: Discussionmentioning

confidence: 99%

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Yang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

show abstract

“…3 MYH9 is dysregulated and serves as an oncogene in many cancers; [4][5][6][7][8][9][10] however, its expression is positively associated with a good prognosis in patients with head and neck squamous cell carcinomas. 11 Moreover, researchers have reported that MYH9 promotes cell invasion and metastasis in gastric cancer, 12,13 facilitates cell growth and metastasis in colorectal cancer and pancreatic cancer, 14,15 and induces drug resistance in neuroblastoma. 16 However, the role of MYH9 in modulating HCC stemness has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

Lin

et al. 2020

Sig Transduct Target Ther

120

View full text Add to dashboard Cite

MYH9 has dual functions in tumors. However, its role in inducing tumor stemness in hepatocellular carcinoma (HCC) is not yet determined. Here, we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma pathogenesis. Importantly, targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in vivo. Mechanistic analysis suggested that MYH9 interacted with GSK3β and reduced its protein expression by ubiquitin-mediated degradation, which therefore dysregulated the β-catenin destruction complex and induced the downstream tumor stemness phenotype, epithelial-mesenchymal transition, and c-Jun signaling in HCC. C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop. X protein is a hepatitis B virus (HBV)-encoded key oncogenic protein that promotes HCC pathogenesis. Interestingly, we observed that HBV X protein (HBX) interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun signaling. Targeting MYH9 blocked HBX-induced GSK3β ubiquitination to activate the β-catenin destruction complex and suppressed cancer stemness and EMT. Based on TCGA database analysis, MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma patients. In clinical samples, high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma patients. These findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration, invasion, growth, and sorafenib resistance in HCC patients. Our study demonstrated that MYH9 is a crucial therapeutic target in HCC.

show abstract

“…It suppresses bladder cancer stem cell proliferation by interacting with the IKK/NF-κB signaling pathway [22] . S100A4-MYH9 axis enhance migration and invasion of cancer cells by inducing epithelial-mesenchymal transition in gastric cancer [23] . Here we indicated that S100A4 expression is closely correlated with tumor progression in CRC, and this study is the first report about the role of S100A4 in promoting CRC growth by enhancing glycolysis.…”

Section: Discussionmentioning

confidence: 99%

S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

show abstract

S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

Cited by 43 publications

References 35 publications

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

Contact Info

Product

Resources

About