Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling–mediated VEGFR2/VEGF‐A overexpression in blood vessel endothelial cells

Wang, Jingshu; Yang, Lina; Fan, Li; Chen, Yaping; Yang, Gong

doi:10.1002/jcb.27480

Cited by 47 publications

(33 citation statements)

References 34 publications

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“…VEGF-A induces the activation of diverse signaling pathways, including the phospholipase C-γ (PLC-γ)/protein kinase C (PKC) pathway via VEGFR2 Tyr1175 phosphorylation (Simons et al 2016) and the phosphoinositide 3-kinase (PI3K)/Akt pathway via VEGFR2 Tyr1175/1173 phosphorylation (Wang et al 2019b). These activated signaling pathways mediated with VEGFR2 modulate the proliferation and migration of TECs, resulting in the facilitation of vasodilation, permeability, and angiogenic processes (Sadremomtaz et al 2018;Wang et al 2019a).…”

Section: Vegf/vegfr Signaling Of Tumor Endothelial Cells In Tumor Angmentioning

confidence: 99%

Pathological angiogenesis and inflammation in tissues

2020

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The role of angiogenesis in the growth of organs and tumors is widely recognized. Vascular–organ interaction is a key mechanism and a concept that enables an understanding of all biological phenomena and normal physiology that is essential for human survival under pathological conditions. Recently, vascular endothelial cells have been classified as a type of innate immune cells that are dependent on the pathological situations. Moreover, inflammatory cytokines and signaling regulators activated upon exposure to infection or various stresses play crucial roles in the pathological function of parenchymal cells, peripheral immune cells, stromal cells, and cancer cells in tissues. Therefore, vascular–organ interactions as a vascular microenvironment or tissue microenvironment under physiological and pathological conditions are gaining popularity as an interesting research topic. Here, we review vascular contribution as a major factor in microenvironment homeostasis in the pathogenesis of normal as well as cancerous tissues. Furthermore, we suggest that the normalization strategy of pathological angiogenesis could be a promising therapeutic target for various diseases, including cancer.

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Section: Vegf/vegfr Signaling Of Tumor Endothelial Cells In Tumor Angmentioning

confidence: 99%

Pathological angiogenesis and inflammation in tissues

2020

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“…3e). The PI3K/AKT pathway is activated in the majority of human cancers, and activation of PI3K/AKT signaling pathway could stimulate angiogenesis by mediating VEGFR2/VEGF-A overexpression 13 . Some other signaling pathways involving angiogenesis, such as the HIF-1 signaling and VEGF signaling pathways were also downregulated, indicating that the angiogenic ability of blood endothelial cells in GGN-ADC cells were weaker than those in SADC cells.…”

Section: Signaling Pathways Related To Cell Proliferation Were Downrementioning

confidence: 99%

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Yang

Shi

et al. 2020

Cell Discov

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As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+ T and CD8+ T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy.

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“…As the critical factor in the course of extrinsic apoptosis, CASP8 was demonstrated to exhibit a potential relationship with breast cancer risk, clinicopathological features, and prognostic outcomes of breast cancer from prior cohort-based analyses [17][18][19]. ITGAX, a component of integrin family, was proven to promote angiogenesis in cancer development and aggressiveness [20]. The associations between PAK1 and breast cancer have been extensively investigated, of which the results indicated that this kind of potential therapeutic target participated in several progressive courses in malignancies [21][22][23].…”

Section: Discussionmentioning

confidence: 99%