Knockout of EGFL6 by CRISPR/Cas9 Mediated Inhibition of Tumor Angiogenesis in Ovarian Cancer

Zhu, Wenhui; Liu, Chunyan; Lu, Tongyi; Zhang, Yinmei; Zhang, Simin; Chen, Qi; Deng, Ning

doi:10.3389/fonc.2020.01451

Cited by 20 publications

(9 citation statements)

References 48 publications

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“…Meanwhile, the PD‐L1/VEGFR2/FAK axis regulated the biological process of angiogenesis. Although other studies clarified the molecular mechanisms of ovarian cancer angiogenesis and metastasis [31, 32], the present study demonstrated that PD‐L1 could act upon VEGFR2, a membrane receptor, to induce ovarian cancer cell angiogenesis and metastasis.…”

Section: Discussioncontrasting

confidence: 67%

Programmed death ligand‐1 regulates angiogenesis and metastasis by participating in the c‐JUN/VEGFR2 signaling axis in ovarian cancer

Yang

Xia

et al. 2021

Cancer Communications

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Background Although programmed cell death‐ligand 1 (PD‐L1) plays a well‐known function in immune checkpoint response by interacting with programmed cell death‐1 (PD‐1), the cell‐intrinsic role of PD‐L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD‐L1 in the progression and metastasis of ovarian cancer. Methods Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD‐L1‐knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD‐L1 in ovarian cancer. Results Our results showed that PD‐L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD‐L1 was identified to directly interact with vascular endothelial growth factor receptor‐2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD‐L1 was found to be regulated by the oncogenic transcription factor c‐JUN at the transcriptional level, which enhanced the expression of PD‐L1 in ovarian cancer. Furthermore, we demonstrated that PD‐L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti‐angiogenesis and the inhibition of cell migration and invasion. Conclusion Our results demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, suggesting that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

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Section: Discussioncontrasting

confidence: 67%

Programmed death ligand‐1 regulates angiogenesis and metastasis by participating in the c‐JUN/VEGFR2 signaling axis in ovarian cancer

Yang

Xia

et al. 2021

Cancer Communications

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“…One factor that has recently captured researchers' attention for its role in angiogenesis is epidermal growth factor-like domain-containing protein 6 (EGFL6) [23]. EGFL6 is a member of the EGF superfamily of proteins; it is also upregulated in tumorigenesis and epithelial-tomesenchymal transition [24][25][26][27]. Xu et al found that osteoblast-like cells secrete EGFL6 in a paracrine manner, triggering EC migration and angiogenesis through activation of the ERK pathway [28].…”

Section: Introductionmentioning

confidence: 99%

EGFL6 regulates angiogenesis and osteogenesis in distraction osteogenesis via Wnt/β-catenin signaling

et al. 2021

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Background Osteogenesis is tightly coupled with angiogenesis during bone repair and regeneration. However, the underlying mechanisms linking these processes remain largely undefined. The present study aimed to test the hypothesis that epidermal growth factor-like domain-containing protein 6 (EGFL6), an angiogenic factor, also functions in bone marrow mesenchymal stem cells (BMSCs), playing a key role in the interaction between osteogenesis and angiogenesis. Methods We evaluated how EGFL6 affects angiogenic activity of human umbilical cord vein endothelial cells (HUVECs) via proliferation, transwell migration, wound healing, and tube-formation assays. Alkaline phosphatase (ALP) and Alizarin Red S (AR-S) were used to assay the osteogenic potential of BMSCs. qRT-PCR, western blotting, and immunocytochemistry were used to evaluate angio- and osteo-specific markers and pathway-related genes and proteins. In order to determine how EGFL6 affects angiogenesis and osteogenesis in vivo, EGFL6 was injected into fracture gaps in a rat tibia distraction osteogenesis (DO) model. Radiography, histology, and histomorphometry were used to quantitatively evaluate angiogenesis and osteogenesis. Results EGFL6 stimulated both angiogenesis and osteogenic differentiation through Wnt/β-catenin signaling in vitro. Administration of EGFL6 in the rat DO model promoted CD31hiEMCNhi type H-positive capillary formation associated with enhanced bone formation. Type H vessels were the referred subtype involved during DO stimulated by EGFL6. Conclusion EGFL6 enhanced the osteogenic differentiation potential of BMSCs and accelerated bone regeneration by stimulating angiogenesis. Thus, increasing EGFL6 secretion appeared to underpin the therapeutic benefit by promoting angiogenesis-coupled bone formation. These results imply that boosting local concentrations of EGFL6 may represent a new strategy for the treatment of compromised fracture healing and bone defect restoration.

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“…EGFL6 is a protein known to be highly expressed in ovarian cancer and proposed to play a key role in promoting tumor angiogenesis. Its knockout markedly inhibited the proliferation, migration, and invasion of SKOV3 cells, as well as promoted apoptosis of tumor cells by downregulating FGF-2/PDGFB signaling pathway [ 140 ].…”

Section: Crispr and Cancermentioning

confidence: 99%

Ten Years of CRISPRing Cancers In Vitro

Capoferri

Filiberti

Faletti

et al. 2022

Cancers

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Cell lines have always constituted a good investigation tool for cancer research, allowing scientists to understand the basic mechanisms underlying the complex network of phenomena peculiar to the transforming path from a healthy to cancerous cell. The introduction of CRISPR in everyday laboratory activity and its relative affordability greatly expanded the bench lab weaponry in the daily attempt to better understand tumor biology with the final aim to mitigate cancer’s impact in our lives. In this review, we aim to report how this genome editing technique affected in the in vitro modeling of different aspects of tumor biology, its several declinations, and analyze the advantages and drawbacks of each of them.

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Knockout of EGFL6 by CRISPR/Cas9 Mediated Inhibition of Tumor Angiogenesis in Ovarian Cancer

Cited by 20 publications

References 48 publications

Programmed death ligand‐1 regulates angiogenesis and metastasis by participating in the c‐JUN/VEGFR2 signaling axis in ovarian cancer

Programmed death ligand‐1 regulates angiogenesis and metastasis by participating in the c‐JUN/VEGFR2 signaling axis in ovarian cancer

EGFL6 regulates angiogenesis and osteogenesis in distraction osteogenesis via Wnt/β-catenin signaling

Ten Years of CRISPRing Cancers In Vitro

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