Cancer-associated fibroblasts-derived VCAM1 induced by H. pylori infection facilitates tumor invasion in gastric cancer

Shen, Jiajia; Zhai, Jing; Qin, You; Zhang, Guoxin; He, Ming-Fang; Yao, Xuequan; Shen, Lizong

doi:10.1038/s41388-020-1197-4

Cited by 51 publications

(49 citation statements)

References 41 publications

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“…In gastric cancer, the abnormal expression of FGF9 in lymph node CAFs was correlated with poor prognosis ( 39 ). H. pylori infection was shown to elevate VCAM1 expression in CAFs, which indicated tumor invasion and progression ( 40 ). IGFBPs facilitate binding of IGF1 to ECM prote in vitro nectin to stimulate proliferation and migration of skin keratinocytes and fibroblasts ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

et al. 2021

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ObjectiveGastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. Insulin-like growth-factor-binding proteins (IGFBPs) were initially identified as passive inhibitors that combined with insulin-like growth factors (IGFs) in serum. However, more recent data have shown that they have different expression patterns and a variety of functions in the development and occurrence of cancers. Thus, their various roles in cancer still need to be elucidated. This study aimed to explore the IGFBPs and their prognostic value as markers in gastric cancer.MethodsOncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier Plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential expression, prognostic value, genetic alteration, and association with immune cell infiltration of IGFPBs in gastric cancer.ResultsExpression levels of IGFBP3, IGFBP4, and IGFBP7 were significantly elevated in gastric cancer tissues, whereas those of IGFBP1 were reduced in normal tissues. IGFBP1/5/7 expression was significantly associated with overall survival whereas IGFBP6/7 expression was significantly correlated with disease-free survival in gastric cancer patients. IGFBP3/5/6/7 were associated with clinical cancer stage. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that IGFBP3/5/7 were mainly enriched in focal adhesion, extracellular matrix structural constituent, cell-substratist junction, extracellular structure, and matrix organization. Stomach adenocarcinoma (STAD) and gastric cancer had more IGFBP1–7 mutations than other tumor types. Hub gene analysis showed that TP53 and IGF2 expression was significantly elevated in STAD patients; PLG, PAPPA, AFP, and CYR61 were associated with overall survival rate; and IGFALS, PLG, IGF1, AHSG, and FN1 were associated with disease-free survival. Finally, IGFBP3–7 were all associated with cancer-associated fibroblast infiltration in STAD, colon adenocarcinoma, and rectal adenocarcinoma.ConclusionOur study provides a comprehensive analysis and selection of IGFBPs as prognostic biomarkers in STAD. This was the first bioinformatic analysis study to describe the involvement of IGFBPs, especially IGFBP7, in gastric cancer development through the extracellular matrix.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

et al. 2021

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“…The detailed experimental method was as described in the previous publication. 36 Cells were stained with DiL (Beyotime, China). Images were analyzed using Image J software.…”

Section: Methodsmentioning

confidence: 99%

“…A 3D sphere BME cell invasion test (Trevigen, Gaithersburg, MD, USA) was used to evaluate the cell invasion. The detailed experimental method was as described in the previous publication 36 . Cells were stained with DiL (Beyotime, China).…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein C‐II induces EMT to promote gastric cancer peritoneal metastasis via PI3K/AKT/mTOR pathway

Wang

Yang

et al. 2021

Clinical & Translational Med

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Background Peritoneal metastasis (PM) occurs frequently in patients with gastric cancer (GC) and confers poor survival. Lipid metabolism acts as a non‐negligible regulator in epithelial–mesenchymal transition (EMT), which is crucial for the metastasis of GC. As apolipoprotein C2 (APOC2) is a key activator of lipoprotein lipase for triglyceride metabolism, the exact mechanism of APOC2 remains largely unknown in GC. Methods Tandem mass tags identified differentially expressed proteins between human PM and GC tissues, and showed that APOC2 overexpressed in PM tissues, which was further confirmed by immunoblotting, immunohistochemistry, and ELISA. Global gene expression changes were identified in APOC2 knockdown cells via RNA‐sequencing. The role of APOC2 in lipid metabolism of GC cells was assessed via the Seahorse XF analyzer and lipid staining assays. The biological role of APOC2 in GC cells was determined by 3D Spheroid invasion, apoptosis, colony formation, wound healing, transwell assay, and mouse models. The interaction between APOC2 and CD36 was analyzed by co‐immunoprecipitation and biolayer interferometry. The underlying mechanisms were investigated using western blot technique. Results APOC2 overexpressed in GC PM tissues. Upregulation of APOC2 correlated with a poor prognosis in GC patients. APOC2 promoted GC cell invasion, migration, and proliferation via CD36‐mediated PI3K/AKT/mTOR signaling activation. Furthermore, APOC2‐CD36 axis upregulated EMT markers of GC cells via increasing the phosphorylation of PI3K, AKT, and mTOR. Knockdown either APOC2 or CD36 inhibited the malignant phenotype of cancer cells, and delayed GC PM progression in murine GC models. Conclusion APOC2 cooperates with CD36 to induce EMT to promote GC PM via PI3K/AKT/mTOR pathway. APOC2‐CD36 axis may be a potential target for the treatment of aggressive GC.

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“…Helicobacter pylori increases the expression of VCAM1 in cancer-associated fibroblasts (CAFs) via JAK/STAT1 signaling pathway in gastric carcinoma, and the level of VCAM1 in patients with gastric cancer is positively correlated with tumor progression and a poor prognosis. Moreover, the interaction between CAF-derived VCAM1 and integrin αvβ1/5 could promote gastric cancer cell invasion both in vitro and in vivo [ 53 ]. In a study of CRC, it was found that chronic inflammation can be promoted via the accumulation of certain bacteria (such as Escherichia coli ) and induce carcinogenesis by cell lethal expansion toxin produced by C. jejuni [ 51 ].…”

Section: Overview Of Microbiota and Autophagymentioning

confidence: 99%

Crosstalk between autophagy and microbiota in cancer progression

Wang

et al. 2021

Mol Cancer

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Autophagy is a highly conserved catabolic process seen in eukaryotes and is essentially a lysosome-dependent protein degradation pathway. The dysregulation of autophagy is often associated with the pathogenesis of numerous types of cancers, and can not only promote the survival of cancer but also trigger the tumor cell death. During cancer development, the microbial community might predispose cells to tumorigenesis by promoting mucosal inflammation, causing systemic disorders, and may also regulate the immune response to cancer. The complex relationship between autophagy and microorganisms can protect the body by activating the immune system. In addition, autophagy and microorganisms can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses involved in cancer progression. Various molecular mechanisms, correlating the microbiota disorders and autophagy activation, control the outcomes of protumor or antitumor responses, which depend on the cancer type, tumor microenvironment and disease stage. In this review, we mainly emphasize the leading role of autophagy during the interaction between pathogenic microorganisms and human cancers and investigate the various molecular mechanisms by which autophagy modulates such complicated biological processes. Moreover, we also highlight the possibility of curing cancers with multiple molecular agents targeting the microbiota/autophagy axis. Finally, we summarize the emerging clinical trials investigating the therapeutic potential of targeting either autophagy or microbiota as anticancer strategies, although the crosstalk between them has not been explored thoroughly.

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Cancer-associated fibroblasts-derived VCAM1 induced by H. pylori infection facilitates tumor invasion in gastric cancer

Cited by 51 publications

References 41 publications

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

Apolipoprotein C‐II induces EMT to promote gastric cancer peritoneal metastasis via PI3K/AKT/mTOR pathway

Crosstalk between autophagy and microbiota in cancer progression

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