Upregulation of SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway

Zhou, Qingqing; Huang, Tingting; Jiang, Zhiyuan; Ge, Chao; Chen, Xiaoxia; Zhang, Lili; Zhao, Fangyu; Zhu, Ming; Chen, Taoyang; Cui, Ying; Li, Hong; Yao, Ming; Li, Jinjun; Tian, Hua

doi:10.1038/s41388-019-1131-9

Cited by 40 publications

(48 citation statements)

References 41 publications

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“…A recent study reports that SNX5 enhances HCC cell proliferation, migration and invasion by inhibiting EGF-mediated EGFR endocytosis and activating the EGFR-ERK1/2 pathway; importantly, its high expression implies poor prognosis of HCC patients. 25 In the research, consistently, it was demonstrated that SNX5 expression was up-regulated in HCC samples, and SNX5 was validated as a target gene of miR-130a-5p and could be positively regulated by circ_0001175. Our work gave a possible explanation to clarify the mechanism of SNX5 dysregulation in HCC.…”

Section: Discussionmentioning

confidence: 96%

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Circ_0001175 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis by Regulating miR-130a-5p

Li¹,

He²,

Chen³

et al. 2020

OTT

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Section: Discussionmentioning

confidence: 96%

“… 24 In HCC, SNX5 high expression is significantly related to vascular invasion, intrahepatic metastasis and the adverse prognosis of the patients; its overexpression also enhances HCC cell proliferation and metastasis. 25 However, the mechanism that triggers the dysregulation of SNX5 in HCC is unclear.…”

Section: Introductionmentioning

confidence: 99%

Circ_0001175 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis by Regulating miR-130a-5p

Li¹,

He²,

Chen³

et al. 2020

OTT

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“…Zhou et al (2020) have reported that SNX5 plays an essential role in the progression of hepatocellular carcinoma (HCC). By using the database of TCGA, SNX5 is increased in HCC tissues compared with adjacent nontumorous tissues.…”

Section: Role Of Snxs In Cancerous/neoplastic Diseasesmentioning

confidence: 99%

Sorting nexins: A novel promising therapy target for cancerous/neoplastic diseases

Yang

Tan

Yang

et al. 2020

Journal Cellular Physiology

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Sorting nexins (SNXs) are a diverse group of cytoplasmic‐ and membrane‐associated phosphoinositide‐binding proteins containing the PX domain proteins. The function of SNX proteins in regulating intracellular protein trafficking consists of endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNX proteins are demonstrated to be involved in several cancerous/neoplastic diseases. Here, we review the accumulated evidence of the molecular structure and biological function of SNX proteins and discuss the regulatory role of SNX proteins in distinct cancerous/neoplastic diseases. SNX family proteins may be a valuable potential biomarker and therapeutic strategy for diagnostics and treatment of cancerous/neoplastic diseases.

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“…SNX10 acts as a tumor suppressor which inhibits colorectal cancer initiation and progression [9].SNX1 expression is signi cantly downregulated in colon cancer [10]. Knockdown of SNX1 expression can signi cantly increase the phosphorylation level of EGFR and promote colon cancer cells proliferation [11].SNX6 predicts poor prognosis and contributes to the metastasis of pancreatic cancer cells via activating epithelial-mesenchymal transition (EMT) [12].SNX27 promotes breast cancer metastasis and the elevated expression of SNX27 could be related to the marginally shorter survival of the patients [13].Our previous research shows that SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway [14].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

Zhou

et al. 2021

Preprint

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Background: Aberrant expression of SNX5 can contribute to tumourigenesis, invasion, and metastasis of several human cancers. However, the clinicopathological and biological significance of SNX5 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of this study was to examine the role of SNX5 in the progression of ccRCC.Methods: Immunohistochemical (IHC), Western blot, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to detect the expression of indicated molecules. The biological role of SNX5 in ccRCC cells was evaluated by CCK8, colony formation, transwell assay, subcutaneous tumor formation as well as veil tail injection. ChIP assay and luciferase reporter assay were used to determine the direct binding of KLF9 to the promoter of the SNX5 gene.Results: SNX5 expression was downregulated in human ccRCC tissues. SNX5 expression was negatively correlated with tumor size, AJCC stage, tumor thrombus of inferior vena cava (IVC) and poor prognosis of ccRCC. Ectopic expression of SNX5 inhibited ccRCC cell proliferation and metastasis whereas knockdown of SNX5 increase these activities both in vitro and in vivo. Mechanistically, overexpression of SNX5 blocked internalization and intracellular trafficking of CD44 in ccRCC cells. Exogenous expression of CD44 partially rescued the inhibitory effects of SNX5 on the proliferation and invasion activity of ccRCC cells. Knockdown of SNX5 in ccRCC cells was associated with epithelial mesenchymal transition (EMT), including the down-regulation of E-cadherin, ZO-1 and Claudin-1 and the concomitant up-regulation of Snail and N-cadherin. In addition, SNX5 inhibited TGF-β-induced migration, invasion and EMT in ccRCC cells. Moreover, we observed a significant correlation between SNX5 expression and E-cadherin levels in ccRCC patients. In addition, KLF9 directly bound to the SNX5 promoter and increased SNX5 transcription. SNX5 expression was closely correlated with KLF9 expression in ccRCC. Moreover, we found that the combination of SNX5 and CD44 or E-cadherin or KLF9 was a more powerful predictor of poor prognosis than either parameter alone.Conclusion: Collectively, our data reveal a mechanism that KLF9-mediated SNX5 expression was associated with poor prognosis via trafficking of CD44 and promoting EMT in ccRCC. SNX5 may be a potential prognostic biomarker and therapeutic target for patients with ccRCC.

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Upregulation of SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway

Cited by 40 publications

References 41 publications

Circ_0001175 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis by Regulating miR-130a-5p

Circ_0001175 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis by Regulating miR-130a-5p

Sorting nexins: A novel promising therapy target for cancerous/neoplastic diseases

Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

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