Cited by 128Angiogenesis and VEGF in CancerCancer Cells and MetastasisGlioma Diagnosis and Treatment

The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.

c-Met–mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma

Open access

Huang, Menggui, Liu, Tianrun, Ma, Peihong, Mitteer, R. Alan, Zhang, Zhenting, Kim, Hyun Jun, Yeo, Eujin, Zhang, Duo, Cai, Peiqiang, Li, Chunsheng, Zhang, Lin, Zhao, Botao, Roccograndi, Laura, O’Rourke, Donald M., Dahmane, Nadia, Gong, Yanqing, Koumenis, Constantinos, Fan, Yi·2016·Journal of Clinical Investigation

DOI 10.1172/jci84876PMC PMC4855929

Open this paper in CoChat — free account Open PDF

Abstract

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci84876

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
The basics of epithelial-mesenchymal transition
Kalluri, R., & Weinberg, R. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39104 · Cited by 10,196
Molecular mechanisms of epithelial–mesenchymal transition
Lamouille, S., Xu, J., & Derynck, R. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3758 · Cited by 8,091
Epithelial–mesenchymal transitions in tumour progression
Thiery, J. P. (2002) · Nature reviews. Cancer · doi:10.1038/nrc822 · Cited by 6,767
A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma
Gilbert, M. R., Dignam, J. J., Armstrong, T. S., Wefel, J. S., Blumenthal, D. T., Vogelbaum, M. A., Colman, H., Chakravarti, A., Pugh, S., Won, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308573 · Cited by 2,834
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
Zeisberg, E. M., Tarnavski, O., Zeisberg, M., Dorfman, A. L., McMullen, J. R., Gustafsson, E., Chandraker, A. K., Yuan, X., Pu, W. T., Roberts, A. B., et al. (2007) · Nature Medicine · doi:10.1038/nm1613 · Cited by 2,251
Genes Expressed in Human Tumor Endothelium
Croix, B. S., Rago, C., Velculescu, V. E., Traverso, G., Romans, K. E., Montgomery, E. A., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., et al. (2000) · Science · doi:10.1126/science.289.5482.1197 · Cited by 1,859
AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients
Batchelor, T. T., Sorensen, A. G., di Tomaso, E., Zhang, W.-T., Duda, D. G., Cohen, K. S., Kozak, K. R., Cahill, D. P., Chen, P.-J., Zhu, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.11.021 · Cited by 1,769
Tumor angiogenesis: molecular pathways and therapeutic targets
Weis, S. M., & Cheresh, D. A. (2011) · Nature Medicine · doi:10.1038/nm.2537 · Cited by 1,762

Show all 49 references

Sorted by citations

Pathological angiogenesis: mechanisms and therapeutic strategies
Dudley, A. C., & Griffioen, A. W. (2023) · Angiogenesis · doi:10.1007/s10456-023-09876-7 · Cited by 571
Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor
Hu, H., Mu, Q., Bao, Z., Chen, Y., Liu, Y., Chen, J., Wang, K., Wang, Z., Nam, Y., Jiang, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.038 · Cited by 345
Challenges in glioblastoma research: focus on the tumor microenvironment
Bikfalvi, A., da Costa, C. A., Avril, T., Barnier, J., Bauchet, L., Brisson, L., Cartron, P., Castel, H., Chevet, É., Chneiweiss, H., et al. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.09.005 · Cited by 326
The role of tumor microenvironment in therapeutic resistance
Son, B., Lee, S., Youn, H., Kim, E., Kim, W., & Youn, B. (2016) · Oncotarget · doi:10.18632/oncotarget.13907 · Cited by 313
Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α
Wang, Q., He, Z., Huang, M., Liu, T., Wang, Y., Xu, H., Duan, H., Ma, P., Zhang, L., Zamvil, S. S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03050-0 · Cited by 293
Self-citation
Molecular Mechanisms of Treatment Resistance in Glioblastoma
Ou, A. C., Yung, W. K. A., & Majd, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010351 · Cited by 283
Endothelial-to-Mesenchymal Transition
Bischoff, J. E. (2019) · Circulation Research · doi:10.1161/circresaha.119.314813 · Cited by 234
Endothelial-to-Mesenchymal Transition in Cancer
Clere, N., Renault, S., & Corre, I. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00747 · Cited by 199
Exosomal miR-155 from M1-polarized macrophages promotes EndoMT and impairs mitochondrial function via activating NF-κB signaling pathway in vascular endothelial cells after traumatic spinal cord injury
Ge, X., Tang, P., Rong, Y., Jiang, D., Lu, X., Ji, C., Wang, J., Huang, C., Duan, A., Liu, Y., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101932 · Cited by 197
Tumor angiogenesis revisited: Regulators and clinical implications
Ronca, R., Benkheil, M., Mitola, S. M. F., Struyf, S., & Liekens, S. (2017) · Medicinal Research Reviews · doi:10.1002/med.21452 · Cited by 198
Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p
Wu, P., Cai, J., Chen, Q., Han, B., Meng, X., Li, Y., Li, Z., Wang, R., Lin, L., Duan, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10025-2 · Cited by 183
MET in glioma: signaling pathways and targeted therapies
Cheng, F., & Guo, D. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1269-x · Cited by 167
EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities
Kahlert, U. D., Joseph, J. V., & Kruyt, F. A. E. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12085 · Cited by 158
Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40
Yang, F., He, Z., Duan, H., Zhang, D., Li, J., Yang, H., Dorsey, J. F., Zou, W., Nabavizadeh, S. A., Bagley, S. J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23832-3 · Cited by 165
Self-citation
PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma
Liu, T., Ma, W., Xu, H., Huang, M., Zhang, D., He, Z., Zhang, L., Brem, S. S., O’Rourke, D. M., Gong, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05982-z · Cited by 162
Self-citation
Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways
Meng, X., Zhao, Y., Han, B. R., Zha, C., Zhang, Y., Li, Z., Wu, P., Qi, T., Jiang, C., Liu, Y., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14036-x · Cited by 149
Targeting PAK4 to reprogram the vascular microenvironment and improve CAR‐T immunotherapy for glioblastoma
Ma, W., Wang, Y., Zhang, R., Yang, F., Zhang, D., Huang, M., Zhang, L., Dorsey, J. F., Binder, Z. A., O’Rourke, D. M., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-00147-8 · Cited by 143
Self-citation
Endothelial cells in tumor microenvironment: insights and perspectives
Leone, P., Malerba, E., Susca, N., Favoino, E., Perosa, F., Brunori, G., Prete, M., & Racanelli, V. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1367875 · Cited by 158
PHGDH-mediated endothelial metabolism drives glioblastoma resistance to chimeric antigen receptor T cell immunotherapy
Zhang, D., Li, A. M., Hu, G., Huang, M., Yang, F., Zhang, L., Wellen, K. E., Xu, X., Conn, C. S., Zou, W., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.010 · Cited by 141
Self-citation
Wnt-mediated endothelial transformation into mesenchymal stem cell–like cells induces chemoresistance in glioblastoma
Huang, M., Zhang, D., Wu, J. Y., Xing, K., Yeo, E., Li, C., Zhang, L., Holland, E. C., Yao, L., Qin, L., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay7522 · Cited by 140
Self-citation
A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials
Silva, E. C. D., Mercier, M.-C., Étienne-Selloum, N., Dontenwill, M., & Choulier, L. (2021) · Cancers · doi:10.3390/cancers13081795 · Cited by 139
Vascular Microenvironment, Tumor Immunity and Immunotherapy
Lamplugh, Z. L., & Fan, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.811485 · Cited by 131
Self-citation
Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications
Rick, J. W., Chandra, A., Ore, C. L. D., Nguyen, A. T., Yagnik, G., & Aghi, M. K. (2019) · Seminars in Oncology · doi:10.1053/j.seminoncol.2019.08.002 · Cited by 125
The role of MET in chemotherapy resistance
Wood, G. E., Hockings, H., Hilton, D. M., & Kermorgant, S. (2021) · Oncogene · doi:10.1038/s41388-020-01577-5 · Cited by 113
Circulating Glioma Cells Exhibit Stem Cell-like Properties
Liu, T., Xu, H., Huang, M., Ma, W., Saxena, D., Lustig, R. A., Alonso‐Basanta, M., Zhang, Z., O’Rourke, D. M., Zhang, L., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0650 · Cited by 116
Self-citation
Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage
Choi, K. J., Nam, J.-K., Kim, J.-H., Choi, S., & Lee, Y. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0439-4 · Cited by 116
EndMT: A promising and controversial field
Hong, L., Du, X., Li, W., Mao, Y., Sun, L., & Li, X. (2018) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2018.07.005 · Cited by 104
Glioblastoma Therapy in the Age of Molecular Medicine
Geraldo, L. H., Garcia, C., da Fonseca, A. C. C., Dubois, L. G., Spohr, T. C. L. D. S. E., Matias, D., Magalhães, E. S. D. C., do Amaral, R. F., da Rosa, B. G., Grimaldi, I., et al. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.11.002 · Cited by 93
Fine‐tuning vascular fate during endothelial–mesenchymal transition
Xiao, L., & Dudley, A. C. (2016) · The Journal of Pathology · doi:10.1002/path.4814 · Cited by 91
Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism
Yang, F., Lee, G., & Fan, Y. (2024) · Angiogenesis · doi:10.1007/s10456-024-09913-z · Cited by 90
Self-citation
FLASH radiation reprograms lipid metabolism and macrophage immunity and sensitizes medulloblastoma to CAR-T cell therapy
Ni, H., Reitman, Z. J., Zou, W., Akhtar, M. N., Paul, R., Huang, M., Zhang, D., Zheng, H., Zhang, R., Ma, R., et al. (2025) · Nature Cancer · doi:10.1038/s43018-025-00905-6 · Cited by 86
Self-citation
MiR-206 inhibits epithelial ovarian cancer cells growth and invasion via blocking c-Met/AKT/mTOR signaling pathway
Dai, C., Xie, Y., Zhuang, X., & Yuan, Z. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.05.077 · Cited by 77
Tumor Vessels Fuel the Fire in Glioblastoma
Rosińska, S., & Gavard, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126514 · Cited by 84
Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma
Cruickshanks, N. A., Zhang, Y., Yuan, F., Pahuski, M., Gibert, M. K., & Abounader, R. (2017) · Cancers · doi:10.3390/cancers9070087 · Cited by 74
Autophagy mediates glucose starvation-induced glioblastoma cell quiescence and chemoresistance through coordinating cell metabolism, cell cycle, and survival
Wang, L. Y., Shang, Z., Zhou, Y., Hu, X., Chen, Y., Fan, Y., Wei, X., Wu, L. L., Liang, Q., Zhang, J., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0242-x · Cited by 75
Self-citation
Dual inhibition of Akt and c‐Met as a second‐line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells
Han, P., Li, H., Jiang, X. L., Zhai, B., Tan, G., Zhao, D., Qiao, H., Liu, B., Jiang, H., & Sun, X. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12039 · Cited by 70
Small-molecule toosendanin reverses macrophage-mediated immunosuppression to overcome glioblastoma resistance to immunotherapy
Yang, F., Zhang, D., Jiang, H., Ye, J., Zhang, L., Bagley, S. J., Winkler, J. D., Gong, Y., & Fan, Y. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abq3558 · Cited by 70
Self-citation
Cancer stem-like cells directly participate in vasculogenic mimicry channels in triple-negative breast cancer
Sun, H., Yao, N., Siqi, C., Linqi, L., Shiqi, L., Zhao, Y., Guanjie, S., Danfang, Z., & Zhi, Y. (2019) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2018.0209 · Cited by 70
A phase 1 and randomized, placebo‐controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872
Galanis, E., Anderson, S. K., Twohy, E. L., Carrero, X. W., Dixon, J. G., Tran, D. D., Jeyapalan, S. A., Anderson, D. M., Kaufmann, T. J., Feathers, R. W., et al. (2019) · Cancer · doi:10.1002/cncr.32340 · Cited by 69
Regulation of Partial and Reversible Endothelial-to-Mesenchymal Transition in Angiogenesis
Fang, J. S., Hultgren, N. W., & Hughes, C. C. W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.702021 · Cited by 65
Cancer-associated fibroblast-derived PAI-1 promotes lymphatic metastasis via the induction of EndoMT in lymphatic endothelial cells
Wei, W.-F., Zhou, H., Chen, P., Huang, X., Huang, L., Liang, L.-J., Guo, C.-H., Zhou, C.-F., Yu, L., Fan, L., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02714-0 · Cited by 64
Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells
Wang, Y., Xu, H., Liu, T., Huang, M., Butter, P.-P., Li, C., Zhang, L., Kao, G. D., Gong, Y., Maity, A. M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.98096 · Cited by 65
Self-citation
Roles of TGF-β signals in tumor microenvironment via regulation of the formation and plasticity of vascular system
Watabe, T., Takahashi, K., Pietras, K., & Yoshimatsu, Y. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.04.007 · Cited by 64
Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance
Azam, Z., To, S. S. T., & Tannous, B. A. (2020) · Advanced Science · doi:10.1002/advs.202002015 · Cited by 62
Microenvironmental regulation of solid tumour resistance to CAR T cell therapy
Lamplugh, Z. L., Wellhausen, N., June, C. H., & Fan, Y. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01229-3 · Cited by 76
Self-citation
Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice
Yang, S., Fang, Y., Ma, Y., Wang, F., Wang, Y., Jia, J., Yang, Y., Sun, W., Zhou, Q., & Li, Z. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70313 · Cited by 61
YAP Orchestrates Heterotypic Endothelial Cell Communication via HGF/c-MET Signaling in Liver Tumorigenesis
Thomann, S., Weiler, S. M. E., Marquard, S., Rose, F., Ball, C. R., Tóth, M., Wei, T., Sticht, C., Fritzsche, S., Roessler, S. K., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0242 · Cited by 50
An immunosuppressive vascular niche drives macrophage polarization and immunotherapy resistance in glioblastoma
Yang, F., Akhtar, M. N., Zhang, D., El-Mayta, R. D., Shin, J., Dorsey, J. F., Zhang, L., Xu, X., Guo, W., Bagley, S. J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj4678 · Cited by 45
Self-citation
ETS transcription factors: Multifaceted players from cancer progression to tumor immunity
Wang, Y., Huang, Z., Sun, M., Huang, W., & Xia, L. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188872 · Cited by 46
Overcoming physical stromal barriers to cancer immunotherapy
Chung, S. W., Xie, Y., & Suk, J. S. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-021-01036-y · Cited by 46
LncRNA MIR155HG Promotes Temozolomide Resistance by Activating the Wnt/β-Catenin Pathway Via Binding to PTBP1 in Glioma
He, X., Sheng, J., Yu, W., Wang, K., Zhu, S., & Liu, Q. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00898-z · Cited by 42
MicroRNA-128-3p Mediates Lenvatinib Resistance of Hepatocellular Carcinoma Cells by Downregulating c-Met
Xu, X., Jiang, W., Han, P., Zhang, J., Tong, L., & Sun, X. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s349369 · Cited by 41
Reprogramming endothelial cells to empower cancer immunotherapy
Cleveland, A. H., & Fan, Y. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.11.002 · Cited by 46
Self-citation
Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity
Baro, M., Sambrooks, C. L., Quijano, A., Saltzman, W. M., & Contessa, J. N. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0792 · Cited by 40
Extracellular proteolysis in glioblastoma progression and therapeutics
Quesnel, A., Karagiannis, G. S., & Filippou, P. S. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188428 · Cited by 40
Current and emerging concepts for systemic treatment of metastatic colorectal cancer
Steup, C., Kennel, K. B., Neurath, M. F., Fichtner-Feigl, S., & Greten, F. R. (2025) · Gut · doi:10.1136/gutjnl-2025-335412 · Cited by 39
TGF-β induces oncofetal fibronectin that, in turn, modulates TGF-β superfamily signaling in endothelial cells
Ventura, E., Weller, M., Macnair, W., Eschbach, K., Beisel, C., Cordazzo, C., Claassen, M., Zardi, L., & Burghardt, I. (2017) · Journal of Cell Science · doi:10.1242/jcs.209619 · Cited by 40
PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation
Rezaei, S., Nikpanjeh, N., Rezaee, A., Gholami, S., Hashemipour, R., Biavarz, N., Yousefi, F., Tashakori, A., Salmani, F., Rajabi, R., et al. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175909 · Cited by 38
NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma
Marín‐Ramos, N. I., Jhaveri, N., Thein, T. Z., Fayngor, R. A., Chen, T. C., & Hofman, F. M. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.10.034 · Cited by 34
Mechanosensory entities and functionality of endothelial cells
Mierke, C. T. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1446452 · Cited by 36
Vascular Detransformation for Cancer Therapy
Fan, Y. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.05.007 · Cited by 28
Self-citation
Verbascoside suppresses the migration and invasion of human glioblastoma cells via targeting c-Met-mediated epithelial-mesenchymal transition
Hei, B., Wang, J., Wu, G., Ouyang, J., & Liu, R.-E. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.05.096 · Cited by 27
The driving mechanism and targeting value of mimicry between vascular endothelial cells and tumor cells in tumor progression
Ma, X., Geng, Z., Wang, S., Yu, Z., Liu, T., Guan, S., Du, S., & Zhu, C. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115029 · Cited by 27
Self-citation
Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma
Areeb, Z., Stuart, S. F., West, A. J., Gomez, J., Nguyen, H. P. T., Paradiso, L., Zulkifli, A., Jones, J., Kaye, A. H., Morokoff, A. P., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-74746-x · Cited by 27
Nanomedicine Revisited: Next Generation Therapies for Brain Cancer
Bhargav, A. G., Mondal, S. K., Garcia, C. A., Green, J. J., & Quiñones‐Hinojosa, A. (2020) · Advanced Therapeutics · doi:10.1002/adtp.202000118 · Cited by 26
Endothelial Cells Promote Docetaxel Resistance of Prostate Cancer Cells by Inducing ERG Expression and Activating Akt/mTOR Signaling Pathway
Zhou, W., Su, Y., Zhang, Y., Han, B., Liu, H., & Wang, X. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.584505 · Cited by 27
Endothelial-to-mesenchymal transition in tumour progression and its potential roles in tumour therapy
Yin, Z., & Wang, L. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2180155 · Cited by 26
The Pleiotropic Role of L1CAM in Tumor Vasculature
Angiolini, F., & Cavallaro, U. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020254 · Cited by 24
SHP2 protects endothelial cell barrier through suppressing VE‐cadherin internalization regulated by MET‐ARF1
Zhang, J., Huang, J., Qi, T., Huang, Y., Lu, Y., Zhan, T., Gong, H., Zhu, Z., Shi, Y., Zhou, J., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201800284r · Cited by 23
Brain-targeted antigen-generating nanoparticles improve glioblastoma prognosis
Wang, W., Zhang, M., Zhang, Q., Mohammadniaei, M., Shen, J., & Sun, Y. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.10.037 · Cited by 22
Lenvatinib for effectively treating antiangiogenic drug-resistant nasopharyngeal carcinoma
Sun, Q., Wang, Y., Ji, H. L., Sun, X., Xie, S., Chen, L., Li, S., Zeng, W., Chen, R., Tang, Q., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05171-3 · Cited by 21
Neovascularization directed by CAVIN1/CCBE1/VEGFC confers TMZ-resistance in glioblastoma
Wang, M., Xia, D., Xu, D., Yin, Y., Xu, F., Zhang, B., Li, K., Yang, Z., & Zou, J. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216593 · Cited by 21
Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis
Ozaki, S., Akihiro, U., Yano, H., Ohsumi, S., Sumida, Y., Hayase, E., Usa, E., Islam, A., Choudhury, M. E., Nishi, Y., et al. (2021) · Neoplasia · doi:10.1016/j.neo.2021.06.001 · Cited by 20
Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression
Giordanengo, L., Proment, A., Botta, V., Picca, F., Munir, H., Tao, J., Olivero, M., Taulli, R., Bersani, F., Sangiolo, D., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136353 · Cited by 20
Endothelial plasticity drives aberrant vascularization and impedes cardiac repair after myocardial infarction
Huang, M., Yang, F., Zhang, D., Lin, M., Duan, H., El-Mayta, R. D., Zhang, L., Qin, L., Shewale, S. V., Pei, L., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00047-3 · Cited by 20
Self-citation
Yes-associated protein promotes endothelial-to-mesenchymal transition of endothelial cells in choroidal neovascularization fibrosis
Zou, R., Xu, Y., Shen, M.-Q., Zhang, X., & Yuan, Y. (2022) · International Journal of Ophthalmology · doi:10.18240/ijo.2022.05.03 · Cited by 18
Co-culture models for investigating cellular crosstalk in the glioma microenvironment
Niu, X., Zhang, Y., & Wang, Y. (2023) · Cancer Pathogenesis and Therapy · doi:10.1016/j.cpt.2023.11.002 · Cited by 21
Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma
Li, J., Xia, D., Zhou, Y., Hu, Y., Yang, Z., Yin, Y., Wang, J., Zhang, B., Gong, L., Li, K., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06743-5 · Cited by 16
Loss of Endothelial Cell Matrix Metalloproteinase 14 Reduces Melanoma Growth and Metastasis by Increasing Tumor Vessel Stability
Kümper, M., Hessenthaler, S., Zamek, J., Niland, S., Pach, E., Mauch, C., & Zigrino, P. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.12.016 · Cited by 16
Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling
Sun, X., Fang, J., Ye, F., Zhang, S., Huang, H., Hou, J., & Wang, T. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.871788 · Cited by 16
Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments
Hovis, G. E. A., Chandra, N. V., Kejriwal, N., Hsieh, K. J.-Y., Chu, A., Yang, I., & Wadehra, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116118 · Cited by 15
Spatial analysis of tissue immunity and vascularity by light sheet fluorescence microscopy
Zhang, D., Cleveland, A. H., Krimitza, E., Han, K., Yi, C., Stout, A. L., Zou, W., Dorsey, J. F., Gong, Y., & Fan, Y. (2024) · Nature Protocols · doi:10.1038/s41596-023-00941-5 · Cited by 17
Self-citation
TGF-β1 Promotes Angiogenesis via Endothelial-to-Mesenchymal Transition in Infantile Hemangioma
Gong, X., Qiu, T., Zhou, J., Yang, K., Xiang, S., Zhang, Z., Lan, Y., Zhang, X., Zhou, Z., Yang, C., et al. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.125.322793 · Cited by 16
Self-citation
Paeoniflorin Inhibits EMT and Angiogenesis in Human Glioblastoma via K63-Linked C-Met Polyubiquitination-Dependent Autophagic Degradation
Liu, Z., Wang, Z., Chen, D., Liu, X., Yu, G., Zhang, Y., Chen, C., Xu, R., Wang, Y., & Liu, R. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.785345 · Cited by 13
Advancing precision medicine in gliomas through single-cell sequencing: unveiling the complex tumor microenvironment
Li, J., Zhang, Y., Liang, C., Yan, X., Hui, X., & Liu, Q. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1396836 · Cited by 13
Novel approaches to combat chemoresistance against glioblastomas
Towner, R. A., Zalles, M., Saunders, D., & Smith, N. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.38 · Cited by 12
Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis
Vliora, M., Nintou, E., Karligiotou, E., Ioannou, L. G., Grillo, E., Mitola, S. M. F., & Flouris, A. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179971 · Cited by 12
Enolase-phosphatase 1 as a novel potential malignant glioma indicator promotes cell proliferation and migration
Su, L., Yang, K., Li, S., Liu, C., Han, J., Zhang, Y., & Xu, G. (2018) · Oncology Reports · doi:10.3892/or.2018.6592 · Cited by 12
Role of vascular endothelium and exosomes in cancer progression and therapy (Review)
Dai, Y., Yao, Y., He, Y., & Hu, X. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5712 · Cited by 11
Mesenchymal Epithelial Transition (MET): A Key Player in Chemotherapy Resistance and an Emerging Target for Potentiating Cancer Immunotherapy
To, K. K. W., & Cho, W. C. S. (2022) · Current Cancer Drug Targets · doi:10.2174/1568009622666220307105107 · Cited by 12
The strange Microenvironment of Glioblastoma
Brisson, L., Geraldo, L. H., Bikfalvi, A., & Mathivet, T. (2023) · Revue Neurologique · doi:10.1016/j.neurol.2023.03.007 · Cited by 11
Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis
Quan, J., Li, Y., Jin, M., Chen, D., Jin, M., & Jin, M. (2017) · Tumor Biology · doi:10.1177/1010428317694572 · Cited by 10
Interleukin 6 and cancer resistance in glioblastoma multiforme
Detchou, D. K. E. D., & Barrie, U. (2024) · Neurosurgical Review · doi:10.1007/s10143-024-02783-5 · Cited by 9
Endothelial transdifferentiation of glioma stem cells: a literature review
Buruiană, A., Florian, I. Ş., Florian, I. A., Şoriţău, O., & Șușman, S. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02031-x · Cited by 9
c-Met Expression Is a Useful Marker for Prognosis Prediction in IDH-Mutant Lower-Grade Gliomas and IDH-Wildtype Glioblastomas
Ohba, S., Yamada, Y., Murayama, K., Pareira, E. S., Sasaki, H., Yamada, S., Abe, M., Hasegawa, M., & Hirose, Y. (2019) · World Neurosurgery · doi:10.1016/j.wneu.2019.03.040 · Cited by 9
Meningeal blood vessel blockage enhances anti-glioblastoma immunity
Gao, Y., Peng, Y., Cheng, J., Zhang, X., Zhong, J., Lu, C., Xing, X., Lai, Y., Sun, H., Zeng, X., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.045 · Cited by 10
Evolutionary Mechanisms of Cancer Suggest Rational Therapeutic Approaches
Balzerano, A., Paccosi, E., & Proietti‐De‐Santis, L. (2021) · Cytogenetic and Genome Research · doi:10.1159/000516530 · Cited by 9
Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy ResponsesPreprint
McAndrews, K. M., Mahadevan, K. K., & Kalluri, R. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041411 · Cited by 8
Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses
Anton, J., Sudibio, S., Handoko, H., Permata, T. B. M., Kodrat, H., Nuryadi, E., Sofyan, H. R., Susanto, E., Mulyadi, R., Aman, R. A., et al. (2021) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2021.22.10.3075 · Cited by 7
TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells
Zhou, H., Liu, M., Shao, T., Xie, P., Zhu, S., Wang, W., Miao, Q., Peng, J., & Zhang, P. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.618540 · Cited by 7

Authors: Huang, M., Liu, T., Ma, P., Mitteer, R. A., Zhang, Z., Kim, H. J., Yeo, E., Zhang, D., Cai, P., Li, C., Zhang, L., Zhao, B., Roccograndi, L., O’Rourke, D. M., Dahmane, N., Gong, Y., Koumenis, C., & Fan, Y.
Affiliations: University of Pennsylvania (US)
Sixth Affiliated Hospital of Sun Yat-sen University (CN)
Shanghai University (CN)
ORCID: Huang, Menggui
Liu, Tianrun
Zhang, Zhenting
Kim, Hyun Jun
Yeo, Eujin
Zhang, Duo
Li, Chunsheng
Zhang, Lin
Zhao, Botao
Roccograndi, Laura
O’Rourke, Donald M.
Dahmane, Nadia
Gong, Yanqing
Koumenis, Constantinos
Fan, Yi
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2016-04-04
Volume: 126
Issue: 5
Pages: 1801-1814
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci84876
PMC: PMC4855929
OpenAlex: W2315035682
Cited by: 128
References: 49
Citations by year: 2026: 13 · 2025: 12 · 2024: 13 · 2023: 15 · 2022: 12 · 2021: 15 · 2020: 16 · 2019: 9 · 2018: 13 · 2017: 7 · 2016: 3
FWCI: 5.54
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
University of Pennsylvania
National Institutes of Health
National Heart, Lung, and Blood Institute (R00HL103792)
National Cancer Institute (R01CA190415)
National Institute of Neurological Disorders and Stroke (R01NS094533)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Keywords: glioblastoma, c-Met, endothelial plasticity, endothelial-to-mesenchymal transition, tumor vascularization, chemoresistance, temozolomide resistance, ETS1, MMP-14, vessel normalization, intratumoral hypoxia, cancer-associated fibroblasts, antivascular therapy
MeSH terms: Temozolomide, Animals, Cell Movement, Dacarbazine, Female, Glioblastoma, Humans, Male, Neovascularization, Pathologic, Cell Hypoxia, Mice, Knockout, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Endothelial Cells, Cell Proliferation, Proto-Oncogene Protein c-ets-1, Mice, Matrix Metalloproteinase 14

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

c-Met–mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks