The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis

Wang, Xin; Wei, Yuan; Wang, Xueqian; Qi, Jialing; Qin, Yinyin; Shi, Yunwei; Zhang, Jie; Gong, Jie; Dong, Zhangji; Liu, Xiaoyu; Sun, Chen; Chai, Renjie; Noble, Ferdinand le; Liu, Dong

doi:10.18632/oncotarget.12793

Cited by 13 publications

(18 citation statements)

References 44 publications

(66 reference statements)

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“…Blocking the AKT signaling resulted in the attenuated capability of migration obviously in breast carcinoma . More interestingly, EGFL6 stimulates activation of AKT signaling in zebrafish . In our study, we found that p‐AKT was downregulated in the shEGFL6 group (Figure A), which means AKT pathway was inhibited when silence EGFL6 in NPC cells.…”

Section: Discussionmentioning

confidence: 56%

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Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Zhu

You

et al. 2018

Cancer Medicine

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Epidermal growth factor‐like domain multiple 6 (EGFL6) is a secreted protein, regulates maintenance and metastasis of cancer cells. Nevertheless, how EGFL6 participates in the progression and tumorigenesis of nasopharyngeal carcinoma (NPC) remains unclear. In our study, EGFL6 was detected highly expressed in 20 NPC tissues compared with normal tissues by IHC assay. Then, the level of EGFL6 in NPC serum and NPC cells was explored through enzyme‐linked immunosorbent assay and western blot, the results consistent with IHC. More interestingly, EGFL6 accelerated the migration and growth of NPC in vitro assays. Considering the mechanism of migration, NPC cells were cultured with AKT activator, revealing EGFL6 facilitated the progression of NPC via AKT. Moreover, the same effect of EGFL6 in promoting NPC growth was proved in nude mice. Furthermore, heat‐shock zebrafish model was established with EGFL6 overexpression. Then, CNE2 cells were injected into the model and cells mass was observed, showing that EGFL6 enhanced the migration and metastasis of NPC. Currently, as the prognosis of NPC is severely affected by distant metastasis, it might be a new therapeutic target toward EGFL6. Taken together, our results suggested that EGFL6 acts as a potential positive regulator in the migration and proliferation of NPC.

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Section: Discussionmentioning

confidence: 56%

“…EGFL6 is an epidermal growth factor‐like protein, it is well known that it plays a series of roles in endothelial cell behaviors and angiogenesis of . Recently, there are some reports prove that EGFL6 involved in the progression of human cancer, such as ovarian cancer, breast cancer, meningioma .…”

Section: Discussionmentioning

confidence: 99%

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Zhu

You

et al. 2018

Cancer Medicine

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“…Regarding the potential mechanisms of EGFL6 in CRC carcinogenesis, most studies have found that EGFL6 acts through the ERK pathway . To the best of our knowledge, this was the first study associating the function of EGFL6 and the Wnt/β‐catenin pathway.…”

Section: Discussionmentioning

confidence: 84%

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β‐catenin pathway

Zhang

Tang

et al. 2019

Molecular Carcinogenesis

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Epidermal growth factor‐like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/β‐catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/β‐catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced β‐catenin in a concentration‐ and time‐dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/β‐catenin inhibitor ICG‐001 increased β‐catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/β‐catenin signaling pathway.

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“… 12 In a zebrafish model, EGFL6 promoted angiogenesis via a mechanism that depended on the RGD domain (Arginyl-glycyl-aspartic acid domain) and on the activation of the Akt and Erk pathways. 18 Loss of EGFL6 decreased the number of endothelial cells and vessels, suggesting that EGFL6 acts as a positive regulator of functional vessel formation. 18 …”

Section: Discussionmentioning

confidence: 98%

“… 18 Loss of EGFL6 decreased the number of endothelial cells and vessels, suggesting that EGFL6 acts as a positive regulator of functional vessel formation. 18 …”

Section: Discussionmentioning

confidence: 98%

Validation of EGFL6 expression as a prognostic marker in patients with lung adenocarcinoma in Taiwan: a retrospective study

et al. 2018

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ObjectiveLung adenocarcinoma is a non-small cell lung cancer, a common cancer in both genders, and has poor clinical outcome. Our aim was to evaluate the role of epidermal growth factor (EGF)-like domain multiple 6 (EGFL6) and its prognostic significance in lung adenocarcinoma.MethodsEGFL6 expression was studied by immunohistochemical staining of specimens from 150 patients with lung adenocarcinoma. The correlation between clinicopathological features and EGFL6 expression was quantitatively analysed. We used Kaplan-Meier analysis and Cox proportional hazard models to examine the prognostic value of EGFL6 in terms of overall survival.ResultsNo significant correlation was found between EGFL6 expression and clinical parameters. However, patients with high levels of EGFL6 expression showed a tendency towards poor prognosis, with borderline statistical significance. Grouping the patients according to a medium age value revealed a significant association between high EGFL6 expression and poor clinical outcome in young patients. This finding was further confirmed by grouping the patients into three groups according to age. HR in patients with high EGFL6 expression was higher in younger patients than in older patients.ConclusionHigh EGFL6 expression may serve as a marker for poor prognosis of lung adenocarcinoma, especially in younger patients.

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The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis

Cited by 13 publications

References 44 publications

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β‐catenin pathway

Validation of EGFL6 expression as a prognostic marker in patients with lung adenocarcinoma in Taiwan: a retrospective study

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