ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer

Jiang, Yingming; Yu, Xihu; Zhao, Yandong; Huang, Jintuan; Li, Tuoyang; Chen, Hao; Zhou, Jianhua; Huang, Zhenze; Yang, Zhaohui

doi:10.3390/biom11040561

Cited by 19 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular mechanisms of S100A16 involving in the tumor metastasis are diverse in various malignant tumors, including pancreatic cancer ( Fang et al, 2021 ; Zhuang et al, 2021 ), leukemia ( Zhang et al, 2019 ), breast cancer ( Zhou et al, 2014 ), and so on. In gastric cancer, decreased S100A16 expression is involved in miR-6884-5p and ADAMTS19 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 19) inhibition of GC cells migration, invasion, and EMT ( Lv et al, 2020 ; Jiang et al, 2021 ), however, the role of S100A16 itself in GC metastasis has not been fully clarified yet.…”

Section: Introductionmentioning

confidence: 99%

Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer

You

Cai

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system, listed as the second cause of cancer-related deaths worldwide. S100 Calcium Binding Protein A16 (S100A16) is an acidic calcium-binding protein associated with several types of tumor progression. However, the function of S100A16 in GC is still not very clear. In this study, we analyzed S100A16 expression with the GEPIA database and the UALCAN cancer database. Meanwhile, 100 clinical GC samples were used for the evaluation of its role in the prognostic analysis. We found that S100A16 is significantly upregulated in GC tissues and closely correlated with poor prognosis in GC patients. Functional studies reveal that S100A16 overexpression triggers GC cell proliferation and migration both in vivo and in vitro; by contrast, S100A16 knockdown restricts the speed of GC cell growth and mobility. Proteomic analysis results reveal a large S100A16 interactome, which includes ZO-2 (Zonula Occludens-2), a master regulator of cell-to-cell tight junctions. Mechanistic assay results indicate that excessive S100A16 instigates GC cell invasion, migration, and epithelial-mesenchymal transition (EMT) via ZO-2 inhibition, which arose from S100A16-mediated ZO-2 ubiquitination and degradation. Our results not only reveal that S100A16 is a promising candidate biomarker in GC early diagnosis and prediction of metastasis, but also establish the therapeutic importance of targeting S100A16 to prevent ZO-2 loss and suppress GC metastasis and progression.

show abstract

Section: Introductionmentioning

confidence: 99%

Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer

You

Cai

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Among these genes, we identified S100A16 using multiple criteria, including its association with glioma, functional validation, and overall survival analysis. S100A16 is involved in various tumors, such as colorectal cancer, bladder cancer, pancreatic cancer, lung adenocarcinoma, cervical cancer, leukemia, and gastric cancer [37][38][39][40][41][42][43]. According to the CGGA database, S100A16 closely correlates with the survival rate of patients with primary gliomas.…”

Section: Discussionmentioning

confidence: 99%

An inhibitor of BRD4, GNE987, inhibits the growth of glioblastoma cells by targeting C-Myc and S100A16

Yang

et al. 2022

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Purpose Among children, glioblastomas (GBMs) are a relatively common type of brain tumor. BRD4 expression was elevated in GBM and negatively correlated with the prognosis of glioma. We investigated the anti-GBM effects of a novel BRD4 inhibitor GNE987. Methods We evaluated the anti-tumor effect of GNE987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, the size of xenografts, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In vitro experiments showed that GNE987 significantly degraded BRD4, inhibited the proliferation of GBM cells, blocked the cell cycle, and induced apoptosis. Similarly, in vivo experiments, GNE987 also inhibited GBM growth as seen from the size of xenografts and Ki67 immunohistochemical staining. Based on Western blotting, GNE987 can significantly reduce the protein level of C-Myc; meanwhile, we combined ChIP-seq with RNA-seq techniques to confirm that GNE987 downregulated the transcription of S100A16 by disturbing H3K27Ac. Furthermore, we validated that S100A16 is indispensable in GBM growth. Conclusion GNE987 may be effective against GBM that targets C-Myc expression and influences S100A16 transcription through downregulation of BRD4.

show abstract

“…Immunohistochemistry and immuno uorescence assay. The biotin-streptavidin horseradish peroxidase (HRP) detection system (ZSGB Bio, China) was used for IHC staining as previously described 22 . In brief, primary rabbit antibody against ADAMTS12 (24934-1-AP, Proteintech, China, 1:1200), VEGF (19003-1-AP, Proteintech, China, 1:2000), cleaved caspase-3 (Cell Signaling Technology, Massachusetts, USA, 1:800), Ki67 (Cell Signaling Technology, Massachusetts, USA, 1:300), and CD31 (Cell Signaling Technology, Massachusetts, USA, 1:200) were incubated with the specimens at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…For immuno uorescence staining, para n-embedded sections were de-para nized by xylene and retrieved via EDTA (1 mM EDTA, 0.05% Tween 20, pH 8.0) for 20 minutes at boiling temperature. The follow-up procedure was the same as in the previous study 22 .…”

Section: Methodsmentioning

confidence: 99%

“…Members of ADAMTS family has been reported to be involved in physiological and pathological processes [16][17][18] . The ectopic expression and abnormal function of ADAMTS family members have been associated with angiogenesis and tumorigenesis [19][20][21][22][23] . Previous studies of ADAMTS12-de cient mice have revealed that ADAMTS12 displays antiangiogenic properties and protects the host from tumor progression 24 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ADAMTS12 mediates vascular abnormality to enhance chemoresistance via the MAPK/VEGF signaling pathway in gastric cancer

Jiang¹,

Huang²,

Huang³

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Purpose: A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) is involved in the angiogenesis and tumorigenesis of gastrointestinal cancer. However, the exact molecular and biological mechanisms of ADAMTS12 in gastric cancer (GC) remain unclear. This study aims to explore the exact underlying mechanisms of ADAMTS12 and provide a biomarker for prognosis and chemotherapy in GC. Methods: Gain- and loss-of-function assays were used to reveal the effect of ADAMTS12 on cell proliferation, migration, invasion, tube formation and chemoresistance in vitro and in vivo. IHC was used to analyze the expression and the correlation between ADAMTS12, VEGF and CD31 in gastric cancer tissues with or without neoadjuvant chemotheraphy. Results: ADAMTS12 promotes cell proliferation, angiogenesis and chemoresistance in vitro and in vivo. ADAMTS12 upregulates VEGF expression through ERK activation, which in turn, promoting angiogenesis and reducing sensitivity to oxaliplatin in GC. In GC tissues, ADAMTS12 was positively correlated with VEGF and microvessel density (MVD). Furthermore, patients with high ADAMTS12 level had poor overall survival (OS) and poor response to neoadjuvant chemotherapy. Conclusion: ADAMTS12 enhances chemoresistance to oxaliplatin in normoxic and hypoxic microenvironments via the MAPK/VEGF signaling pathway in GC. High ADAMTS12 levels have prognostic significance for poor survival, and indicator of vascular abnormality and chemoresistance in GC.

show abstract

ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer

Cited by 19 publications

References 30 publications

Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer

Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer

An inhibitor of BRD4, GNE987, inhibits the growth of glioblastoma cells by targeting C-Myc and S100A16

ADAMTS12 mediates vascular abnormality to enhance chemoresistance via the MAPK/VEGF signaling pathway in gastric cancer

Contact Info

Product

Resources

About