STAM2 knockdown inhibits proliferation, migration, and invasion by affecting the JAK2/STAT3 signaling pathway in gastric cancer

2021 ◽  
Author(s):  
Yang Yang ◽  
Q i Zhang ◽  
Jiakui Liang ◽  
Meiyuan Yang ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Mammalian Cells ◽  
Migration And Invasion ◽  
Boyden Chamber ◽  
Pathway Enrichment Analysis ◽  
Stat3 Signaling ◽  
Advanced Tumor ◽  
Stat3 Signaling Pathway ◽  
Tumor Node Metastasis Stage

Abstract Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which regulates receptor signaling and trafficking of mammalian cells. However, its role in gastric cancer (GC) remains undiscovered. In this study, we aimed to investigate the functions of STAM2 in GC. The mRNA and protein expression levels of STAM2 were measured by quantitative real-time PCR, western blot analysis, and immunohistochemistry. STAM2 was stably silenced in AGS and HGC-27 cells using small interfering RNA. The function of STAM2 in GC cells was further investigated by CCK-8 assay, EdU incorporation assay, flow cytometry, and scratch wound healing and Boyden chamber assays. Additionally, we conducted biological pathway enrichment analysis and rescue assays to explore the effects of STAM2 on JAK/STAT signaling pathway. Our results showed that STAM2 is remarkably highly expressed in GC tissues and cells, and overexpressed STAM2 is correlated with tumor size, advanced tumor node metastasis stage, and poor prognosis. In addition, STAM2 knockdown could significantly inhibit proliferation, block cell cycle, and restrain migration and invasion capabilities of GC cells. Mechanistically, we found that STAM2 knockdown effectively decreased the expressions of MMP2 and MMP9 and the phosphorylation levels of JAK2 and STAT3. Taken together, this study revealed that STAM2 knockdown could suppress malignant process by targeting the JAK2/STAT3 signaling pathway in GC.

scholarly journals 3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Chakrabhavi Dhananjaya Mohan ◽  
Min Hee Yang ◽  
Shobith Rangappa ◽  
Arunachalam Chinnathambi ◽  
Sulaiman Ali Alharbi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Tyrosine Kinases ◽  
Present Report ◽  
Migration And Invasion ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Substantial Toxicity ◽  
Transcription 3 ◽  
Constitutive Phosphorylation

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

scholarly journals Dynasore suppresses cell proliferation, migration, and invasion and enhances the antitumor capacity of cisplatin via STAT3 pathway in osteosarcoma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Binlong Zhong ◽  
Deyao Shi ◽  
Fashuai Wu ◽  
Shangyu Wang ◽  
Hongzhi Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Migration And Invasion ◽  
G1 Arrest ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Candidate Drug

Abstract Osteosarcoma (OS) is the most common malignant bone tumor. The prognosis of metastatic and recurrent OS patients still remains unsatisfactory. Cisplatin reveals undeniable anti-tumor effect while induces severe side effects that threatening patients’ health. Dynasore, a cell-permeable small molecule that inhibits dynamin activity, has been widely studied in endocytosis and phagocytosis. However, the anti-tumor effect of dynasore on OS has not yet been ascertained. In the present study, we suggested that dynasore inhibited cell proliferation, migration, invasion, and induced G0/G1 arrest of OS cells. Besides, dynasore repressed tumorigenesis of OS in xenograft mouse model. In addition, we demonstrated that dynasore improved the anti-tumor effect of cisplatin in vitro and in vivo without inducing nephrotoxicity and hepatotoxicity. Mechanistically, dynasore repressed the expression of CCND1, CDK4, p-Rb, and MMP-2. Furthermore, we found that dynasore exerts anti-tumor effects in OS partially via inhibiting STAT3 signaling pathway but not ERK-MAPK, PI3K-Akt or SAPK/JNK pathways. P38 MAPK pathway served as a negative regulatory mechanism in dynasore induced anti-OS effects. Taken together, our study indicated that dynasore does suppress cell proliferation, migration, and invasion via STAT3 signaling pathway, and enhances the antitumor capacity of cisplatin in OS. Our results suggest that dynasore is a novel candidate drug to inhibit the tumor growth of OS and enhance the anti-tumor effects of cisplatin.

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