Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer

Ma, Jiachi; Sun, Xuejing; Su, Hongling; Chen, Quan; Guo, Tiankang; Li, Yuan; Chen, Xiao-Chang; Guo, Jin; Gong, Zhuwen; Zhao, Xiaodan; Qi, Jianbo

doi:10.3748/wjg.v23.i28.5167

Cited by 49 publications

(39 citation statements)

References 39 publications

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“…With respect to other factors implicated in angiogenesis, we found that both docetaxel and vinorelbine increased AKT1, ERK1, ERK2, CXCL6, NOS3 and CCL2 transcription. CXCL6 stimulates breast cancer development triggering the phosphorylation of ERK1 and ERK2, thus inducing migration and growth of endothelial cells 69 . CCL2 turns human breast epithelial cells into a more aggressive and invasive phenotype 70 .…”

Section: Discussionmentioning

confidence: 99%

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

González-González

González

Rueda

et al. 2020

Sci Rep

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chemotherapeutics are sometimes administered with drugs, like antiangiogenic compounds, to increase their effectiveness. Melatonin exerts antitumoral actions through antiangiogenic actions. We studied if melatonin regulates the response of HUVECs to chemotherapeutics (docetaxel and vinorelbine). The inhibition that these agents exert on some of the processes involved in angiogenesis, such as, cell proliferation, migratory capacity or vessel formation, was enhanced by melatonin. Regarding to estrogen biosynthesis, melatonin impeded the negative effect of vinorelbine, by decreasing the activity and expression of aromatase and sulfatase. Docetaxel and vinorelbine increased the expression of VEGF-A, VEGF-B, VEGF-C, VEGFR-1, VEGFR-3, ANG1 and/or ANG-2 and melatonin inhibited these actions. Besides, melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1, ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. In CAM assay melatonin inhibited new vascularization in combination with chemotherapeutics. Melatonin further enhanced the chemotherapeutics-induced inhibition of p-AKt and p-eRK and neutralized the chemotherapeuticscaused stimulatory effect on HUVECs permeability by modifying the distribution of VE cadherin. Our results confirm that melatonin blocks proangiogenic and potentiates antiangiogenic effects induced by docetaxel and vinorelbine enhancing their antitumor effectiveness.The development of new blood vessels is needed to provide oxygen and nutrients to the tumor cells and a way to escape from the primary site 1 . Angiogenesis is a main step in tumor growth and antiangiogenic agents are considered an interesting complementary strategy in cancer therapy 2 . Angiogenesis is a multi-step process: endothelial cell activation by growth factors, degradation of capillary wall by proteinases, formation of a branch point in the vessel wall, migration of endothelial cells and proliferation and reorganisation of endothelial cells to form tubules. In tumors, the interaction between endothelial cells and the microenvironment stimulates endothelial cells to proliferate, migrate and form a branching network of tubes 3 . A balance between angiogenic activating and inhibiting factors regulates the evolution of endothelial cells from a quiescent to a proangiogenic stage 2 . Among the principal proangiogenic factors are vascular endothelial growth factor (VEGF) and angiopoietins (ANG) 4,5 . Angiogenesis depends on the coordinated balance in time between the production of VEGF and angiopoietins 6 .Melatonin, produced in the pineal gland, has antitumor effects in different cancer types, especially hormone-dependent tumors 7-10 . Melatonin oncostatic actions are exerted through different mechanisms, such as: indirect effects through a down-regulation of gonadal estrogens 11 ; direct antiestrogenic actions at the tumor cell ...

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Section: Discussionmentioning

confidence: 99%

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

González-González

González

Rueda

et al. 2020

Sci Rep

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“…A large number of articles have confirmed that PI3K/AKT/mTOR pathway plays an important role in the tumor, and its targeted inhibition has become a hot topic in drug research. [24][25][26][27][28][29] In endometrial carcinoma, the role of PI3K/AKT/ mTOR pathway has been extensively studied. This pathway is associated with the promotion of tumor properties, poor prognosis, and traditional drug resistance, and targeted inhibition of PI3K/AKT/ mTOR pathway in the treatment of endometrial carcinoma has shown excellent results, in both preclinical and clinical trials.…”

Section: Discussionmentioning

confidence: 99%

lncRNA DLEU1 contributes to tumorigenesis and development of endometrial carcinoma by targeting mTOR

Wang

Chen

et al. 2018

Molecular Carcinogenesis

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lncRNA DLEU1 as a non-coding gene, involves in the occurrence and development of multiple tumors. However, there is no related report in endometrial carcinoma. In order to focus on the role and mechanism of lncRNA DLEU1 in endometrial carcinoma, we used qRT-PCR to detect the expression of lncRNA DLEU1 and found that lncRNA DLEU1 was highly expressed in endometrial carcinoma compared to normal endometrium. Moreover, compared to Ishikawa and KLE, lncRNA DLEU1 was higher in HEC-1B. In addition, up-regulation of lncRNA DLEU1 promoted cell viability, migration, invasion, and reduced the proportion of apoptosis. Otherwise, down-regulation of lncRNA DLEU1 produced opposite results. Xenograft nude mice model assay showed that lncRNA DLEU1 can promote tumorigenesis in vivo. RiP confirmed that lncRNA DLEU1 could bind to mTOR. The rescue experiments revealed that silence of mTOR after up-regulation of lncRNA DLEU1 resulted in decrease of cell viability, migration, and invasion and increase of apoptosis. The expression changes of PI3K, AKT1, p70S6K, rpS6, GSK3β, STAT3, and Bcl-xl were consistent with lncRNA DLEU1 and mTOR in Western blot. Thus, we suggest that lncRNA DLEU1 combines with mTOR and then increases the expression of PI3K/AKT/mTOR pathway to promote endometrial carcinoma tumorigenesis and progression. The present discovery has probability to provide a biomarker and lay the foundation for targeted therapy of endometrial carcinoma.

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“…Down-regulation of CXCL2 destroyed the proliferation and colony formation in CRC cells [55]. Moreover, CXCL2 remarkably promoted the proliferation and migration of HUVECs [56]. But the qPCR results showed no significant difference in CXCL2 expression between HCT116 and NCM460 cell lines.…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis

Liu¹,

Li²,

Dong

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most lethal malignancy in the world, wherein colon adenocarcinoma (COAD) is the most prevalent type of CRC.Exploring biomarkers is important for the diagnosis, treatment, and prevention of COAD. Methods: We used GEO2R and Venn online software for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software, real-time PCR and immunohistochemistry. Results: In this study, we screened 323 common differentially expressed genes from four GSE datasets. Furthermore, four hub genes were selected for survival correlation analysis and expression level verification, three of which were shown to be statistically significant. Conclusion: Our study suggests that SERPINE1, SPP1 and TIMP1 may be biomarkers closely related to the prognosis of CRC patients.

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Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer

Cited by 49 publications

References 39 publications

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

lncRNA DLEU1 contributes to tumorigenesis and development of endometrial carcinoma by targeting mTOR

Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis

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