STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway

Zhang, Bin; Zhao, Zhi‐Wen; Wang, Youpeng; Guo, Tingting; He, Mingyang; Guan, Ge; Peng, Pai; Cai, Jinzhen; Zhang, Bingyuan; Liu, Xutao; Song, Qiaoling

doi:10.14218/jcth.2022.00276

Cited by 4 publications

(3 citation statements)

References 42 publications

(41 reference statements)

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“…3B). Interestingly, the most significant positive relationships were seen to proteins with known roles in cancer progression and development: protein YIF1A 38 , ubiquitin associated protein 1 (UBAP1) 39 , DDRGK domain-containing protein 1 40 and syntaxin-5 (STX5) 41 . This is relevant to reports of poor glycemic control being associated with and increased risk of multiple cancers 42 .…”

Section: Resultsmentioning

confidence: 99%

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Kolic

Sun

Cen

et al. 2023

Preprint

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Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition.We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people's islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.

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Section: Resultsmentioning

confidence: 99%

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Kolic

Sun

Cen

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Interestingly, the most significant positive relationships were seen to proteins with known roles in cancer progression and development: protein YIF1A, 38 ubiquitin-associated protein 1 (UBAP1), 39 DDRGK domain-containing protein 1 (DDRGK1), 40 and syntaxin-5 (STX5). 41 Poor glycemic control is associated with increased risk of multiple cancers. 42 …”

Section: Resultsmentioning

confidence: 99%

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Kolic,

Sun,

Cen

et al. 2024

Cell Metabolism

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“…Multiple oncogenic properties have been widely linked to the expression of SNARE proteins ( 49 ). Moreover, STX5 has been recently described to modulate PI3K/mTOR pathway activation, subsequently restraining cell adhesion and thus favoring metastasis in hepatocellular carcinoma ( 50 ). Although STX5-mediated pro-tumorigenic mechanisms in HGSOC remain to be elucidated, our results demonstrate that expression of STX5 in PFD-sEVs is associated with tumor progression and, to a lesser extent, with the degree of response to chemotherapy, which would be in line with analogous functions observed in other members of its protein family ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer

Quiralte,

Barquín,

Yagüe-Fernández

et al. 2024

Journal of Clinical Investigation

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Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid–derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

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STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway

Abstract: Background and Aims: Syntaxin 5 (STX5) is a member of the syntaxin or target-soluble SNAP receptor (t-SNARE) fam

Cited by 4 publications

References 42 publications

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer

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