Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Potent Target for Breast Cancer Therapy

Lian, Caixia; Ruan, Lingling; Shang, Dongsheng; Wu, Yanfang; Lu, Yongjin; Lü, Peng; Yang, Yuhua; Wei, Yajun; Dong, Xiang Da; Ren, Dewan; Chen, Keping; Liu, Hanqing; Tu, Zhigang

doi:10.1089/cbr.2015.1956

Cited by 14 publications

(4 citation statements)

References 96 publications

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“…Growth factor binding is found in the progression of various cancers. For example, heparin-binding epidermal growth factor-like growth factor acts as a potent target for breast cancer therapy [23]. Voltage-gated Na+ channel…”

Section: Discussionmentioning

confidence: 99%

Association between SNAP25 and human glioblastoma multiform: a comprehensive bioinformatic analysis

Yin

Wang

et al. 2020

Bioscience Reports

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Background: Glioblastoma multiforme (GBM) is a most common aggressive malignant brain tumor. In recent years, targeted therapy has been increasingly applied in GBM treatment. Methods: In the present study, GSE22866 was downloaded from gene expression omnibus (GEO). The genomic and clinical data were obtained from TCGA. The differentially expressed genes (DEGs) were identified and functional analysis was performed using clusterprofiler. Then, the co-expression network for the DEGs was established using the “WGCNA” package. Next, the protein–protein interaction (PPI) was assessed using Search Tool for the Retrieval of Interacting Genes Database (STRING) and hub modules in Cytoscape were screened. The Venn diagram was plotted to showcase the overlapped hub DEGs in PPI network and TCGA. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the risk score of each patient. Validations of the hub gene were completed in other databases. Results: Functional analysis of the DEGs verified the involvement of DEGs in growth factor binding and gated channel activity. Among the 10 GBM-related modules, the red one displayed the strongest tie with GBM. VAMP2 was filtered out as the most intimate protein. The PPI network and TCGA were comprehensively analyzed. Finally, SNAP25 was identified as a real hub gene positively correlated with GBM prognosis. The result was validated by GEPIA, ONCOMINE database and qRT-PCR. Conclusions: SNAP25 might act as a GBM suppressor and a biomarker in GBM treatment.

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Section: Discussionmentioning

confidence: 99%

Association between SNAP25 and human glioblastoma multiform: a comprehensive bioinformatic analysis

Yin

Wang

et al. 2020

Bioscience Reports

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“…Paracrine signalling is a main form of intercellular communication, by which cells respond to the factors produced from nearby cells [ 26 , 27 ]. It has been shown that HB-EGF plays a variety of roles in cell proliferation, migration and inflammation through paracrine action [ 28 , 29 ]. Whether such a paracrine mechanism between leader cells coordinates their polarization and behaviour under EFs also needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

et al. 2023

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Background Endogenous electric fields (EFs) play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound healing. Although polarization of leadercells is essential for collective migration, the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain unclear. This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets. Methods Collective migration of the human epidermal monolayer (human immortalized keratinocytes HaCaT) under EFs was observed via time-lapse microscopy. The involvement of tetraspanin-29 (CD9) in EF-induced fibrous actin (F-actin) polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic manipulation. Blocking, rescue and co-culture experiments were conducted to explore the downstream signalling of CD9. Results EFs guided the coordinated collective migration of the epithelial monolayer to the anode, with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration. F-actin polarization, as expected, played an essential role in pseudopod formation in leader cells under EFs. By confocal microscopy, we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs. Interestingly, genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal monolayer. Mechanistically, CD9 determined the polarization of F-actin in leader cells by downregulating a disintegrin and metalloprotease 17/heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor (ADAM17/HB-EGF/EGFR) signalling. The abolished polarization of leader cells due to CD9 overexpression could be restored in a co-culture monolayer where normal cells and CD9-overexpressing cells were mixed; however, this restoration was eliminated again by the addition of the HB-EGF-neutralizing antibody. Conclusion CD9 functions as a key regulator in the EF-guided collective migration of the epidermal monolayer by controlling and coordinating the polarization of leader cells through ADAM17/HB-EGF/EGFR signalling.

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“…HB-EGF is a ligand in the epidermal growth factor receptor (EGFR) family [ 5 ], and its expression is mostly enhanced in breast cancer tissues compared to other EGFR ligands [ 6 ]. Previous studies have shown that HB-EGF plays a crucial role in mammary carcinoma, especially in promoting angiogenesis, local invasion and tumor metastasis [ 5 , 7 ]. Moreover, the elevated expression of HB-EGF is correlated with a higher histological grade, higher rate of lymph node metastasis and worse overall survival in breast cancer patients [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that HB-EGF plays a crucial role in mammary carcinoma, especially in promoting angiogenesis, local invasion and tumor metastasis [ 5 , 7 ]. Moreover, the elevated expression of HB-EGF is correlated with a higher histological grade, higher rate of lymph node metastasis and worse overall survival in breast cancer patients [ 6 , 7 ]. Furthermore, HB-EGF promotes cancer development in association with proangiogenic platelet-derived growth factors (PDGFs) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Concentration of Selected Angiogenesis-Related Molecules Differs among Molecular Subtypes, Body Mass Index and Menopausal Status in Breast Cancer Patients

Balalis

Tsakogiannis²,

Kalogera³

et al. 2022

JCM

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Background: Angiogenesis is a hallmark of breast cancer (BC) and is mediated by the vascular endothelial growth factor (VEGF) signaling axis. It is regulated by different proangiogenic factors, including platelet-derived growth factor-CC (PDGF-CC) and heparin-binding EGF-like growth factor (HB-EGF), as well as co-receptors, such as neuropilin-1, which could have prognostic implications in BC patients. Patients and methods: We assessed the serum levels of VEGF, HB-EGF, PDGF-CC and neuropilin-1 in 205 patients with early BC (invasive, n = 187; in situ, n = 18) and in 31 healthy donors (HD) and investigated the potential associations with clinical and histopathological parameters. Results: VEGF serum levels were significantly higher in patients with invasive versus ductal carcinomas in situ. PDGF-CC serum concentrations varied among BC molecular subtypes. Furthermore, we observed a differential expression of most biomarkers between overweight/obese (body mass index (BMI) ≥ 25 kg/m2) and non-obese patients among the BC molecular subtypes. Finally, the classification of subjects according to menopausal status revealed a significant difference in specific biomarker levels between patients and HD. Conclusion: The serum concentrations of angiogenic molecules differ among breast cancer molecular subtypes and are affected by the BMI and menopausal status, which could have possible clinical or prognostic implications.

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Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Potent Target for Breast Cancer Therapy

Cited by 14 publications

References 96 publications

Association between SNAP25 and human glioblastoma multiform: a comprehensive bioinformatic analysis

Association between SNAP25 and human glioblastoma multiform: a comprehensive bioinformatic analysis

CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

Serum Concentration of Selected Angiogenesis-Related Molecules Differs among Molecular Subtypes, Body Mass Index and Menopausal Status in Breast Cancer Patients

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