The Role of Rho GTPases in VEGF Signaling in Cancer Cells.

Vascular Endothelial Growth Factor A; rho GTP-Binding Proteins; Animals; Carcinogenesis/metabolism; Carcinogenesis/pathology; Humans; Neoplasms/metabolism; Neoplasms/pathology; Neovascularization, Pathologic/metabolism; Neovascularization, Pathologic/pathology; Signal Transduction/physiology; Vascular Endothelial Growth Factor A/metabolism; rho GTP-Binding Proteins/metabolism; Carcinogenesis; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Pathology and Forensic Medicine; Molecular Medicine; Cell Biology; Cancer Research; General Medicine

Abstract :

[en] Vascular endothelial growth factors (VEGFs) consist of five molecules (VEGFA through D as well as placental growth factor) which are crucial for regulating key cellular and tissue functions. The role of VEGF and its intracellular signaling and downstream molecular pathways have been thoroughly studied. Activation of VEGF signal transduction can be initiated by the molecules' binding to two classes of transmembrane receptors: (1) the VEGF tyrosine kinase receptors (VEGF receptors 1 through 3) and (2) the neuropilins (NRP1 and 2). The involvement of Rho GTPases in modulating VEGFA signaling in both cancer cells and endothelial cells has also been well established. Additionally, different isoforms of Rho GTPases, namely, RhoA, RhoC, and RhoG, have been shown to regulate VEGF expression as well as blood vessel formation. This review article will explore how Rho GTPases modulate VEGF signaling and the consequences of such interaction on cancer progression.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

El Baba, Nada; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

Farran, Mohammad ; Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology ; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

Khalil, Elie Abi; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

Jaafar, Leila; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

Fakhoury, Isabelle ; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

El-Sibai, Mirvat ; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

Language :

English

Title :

The Role of Rho GTPases in VEGF Signaling in Cancer Cells.

Publication date :

2020

Journal title :

Analytical Cellular Pathology

ISSN :

2210-7177

eISSN :

2210-7185

Publisher :

Hindawi Limited, New York, United States

Volume :

2020

Pages :

2097214

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://downloads.hindawi.com/journals/acp/2020/2097214.pdf

Available on ORBi :

since 23 April 2024

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Bibliography

A. S. Chung and N. Ferrara, "Developmental and pathological angiogenesis, " Annual Review of Cell and Developmental Biology, vol. 27, no. 1, pp. 563-584, 2011.
M. Simons, E. Gordon, and L. Claesson-Welsh, "Mechanisms and regulation of endothelial VEGF receptor signalling, " Nature Reviews Molecular Cell Biology, vol. 17, no. 10, pp. 611-625, 2016.
P. Carmeliet and R. K. Jain, "Angiogenesis in cancer and other diseases, " Nature, vol. 407, no. 6801, pp. 249-257, 2000.
L. Zhao, G. Xu, J. Zhou et al., "The effect of RhoA on human umbilical vein endothelial cell migration and angiogenesis in vitro, " Oncology Reports, vol. 15, no. 5, pp. 1147-1152, 2006.
J. Folkman, "Angiogenesis in cancer, vascular, rheumatoid and other disease, " Nature Medicine, vol. 1, no. 1, pp. 27-31, 1995.
N. Sellami, L. B. Lamine, A. Turki et al., "Association of VEGFA variants with altered VEGF secretion and type 2 diabetes: A case-control study, " Cytokine, vol. 106, pp. 29-34, 2018.
H. P. Gerber, V. Dixit, and N. Ferrara, "Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells, " The Journal of Biological Chemistry, vol. 273, no. 21, pp. 13313-13316, 1998.
H. P. Gerber, A. McMurtrey, J. Kowalski et al., "Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation, " The Journal of Biological Chemistry, vol. 273, no. 46, pp. 30336-30343, 1998.
B. J. Nieves, P. A. D'Amore, and B. A. Bryan, "The function of vascular endothelial growth factor, " BioFactors, vol. 35, no. 4, pp. 332-337, 2009.
N. Nishida, H. Yano, T. Nishida, T. Kamura, and M. Kojiro, "Angiogenesis in cancer, " Vascular Health and Risk Management, vol. 2, no. 3, pp. 213-219, 2006.
B. A. Bryan and P. A. D'Amore, "What tangled webs they weave: Rho-GTPase control of angiogenesis, " Cellular and Molecular Life Sciences, vol. 64, no. 16, pp. 2053-2065, 2007.
B. A. Bryan, E. Dennstedt, D. C. Mitchell et al., "RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis, " The FASEB Journal, vol. 24, no. 9, pp. 3186-3195, 2010.
W. Wang, F. Wu, F. Fang, Y. Tao, and L. Yang, "RhoC is essential for angiogenesis induced by hepatocellular carcinoma cells via regulation of endothelial cell organization, " Cancer Science, vol. 99, no. 10, pp. 2012-2018, 2008.
A. B. Jaffe and A. Hall, "Rho GTPases: Biochemistry and biology, " Annual Review of Cell and Developmental Biology, vol. 21, pp. 247-269, 2005.
A. L. Bishop and A. Hall, "Rho GTPases and their effector proteins, " Biochemical Journal, vol. 348, no. 2, pp. 241-255, 2000.
J. J. Bravo-Cordero, V. P. Sharma, M. Roh-Johnson et al., "Spatial regulation of RhoC activity defines protrusion formation in migrating cells, " Journal of Cell Science, vol. 126, Part 15, pp. 3356-3369, 2013.
C. D. Nobes and A. Hall, "Rho, Rac and cdc 42 GTPases: Regulators of actin structures, cell adhesion and motility, " Biochemical Society Transactions, vol. 23, no. 3, pp. 456-459, 1995.
C. D. Nobes and A. Hall, "Rho, rac, and cdc 42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia, " Cell, vol. 81, no. 1, pp. 53-62, 1995.
A. Hall, "Rho GTPases and the actin cytoskeleton, " Science, vol. 279, no. 5350, pp. 509-514, 1998.
A. Hall and C. D. Nobes, "Rho GTPases: Molecular switches that control the organization and dynamics of the actin cytoskeleton, " Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, vol. 355, no. 1399, pp. 965-970, 2000.
N. A. Hotchin and A. Hall, "Regulation of the actin cytoskeleton, integrins and cell growth by the Rho family of small GTPases, " Cancer Surveys, vol. 27, pp. 311-322, 1996.
B. H. Fryer and J. Field, "Rho, Rac, Pak and angiogenesis: Old roles and newly identified responsibilities in endothelial cells, " Cancer Letters, vol. 229, no. 1, pp. 13-23, 2005.
M. Holinstat, N. Knezevic, M. Broman, A. M. Samarel, A. B. Malik, and D. Mehta, "Suppression of RhoA activity by focal adhesion kinase-induced activation of p190RhoGAP: Role in regulation of endothelial permeability, " The Journal of Biological Chemistry, vol. 281, no. 4, pp. 2296-2305, 2006.
D. Mehta and A. B. Malik, "Signaling mechanisms regulating endothelial permeability, " Physiological Reviews, vol. 86, no. 1, pp. 279-367, 2006.
E. Monaghan-Benson and K. Burridge, "The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species, " The Journal of Biological Chemistry, vol. 284, no. 38, pp. 25602-25611, 2009.
P. Vader, R. van der Meel, M. H. Symons et al., "Examining the role of Rac 1 in tumor angiogenesis and growth: A clinically relevant RNAi-mediated approach, " Angiogenesis, vol. 14, no. 4, pp. 457-466, 2011.
R. van der Meel, M. H. Symons, R. Kudernatsch et al., "The VEGF/Rho GTPase signalling pathway: A promising target for anti-angiogenic/anti-invasion therapy, " Drug Discovery Today, vol. 16, no. 5-6, pp. 219-228, 2011.
M. Bisht, D. C. Dhasmana, and S. S. Bist, "Angiogenesis: Future of pharmacological modulation, " Indian Journal of Pharmacology, vol. 42, no. 1, pp. 2-8, 2010.
Y. Maeshima, "Angiogenesis and cancer, " in Apoptosis, Cell Signaling, and Human Diseases, R. Srivastava, Ed., pp. 35-61, Humana Press, 2007.
R. K. Jain, E. di Tomaso, D. G. Duda, J. S. Loeffler, A. G. Sorensen, and T. T. Batchelor, "Angiogenesis in brain tumours, " Nature Reviews Neuroscience, vol. 8, no. 8, pp. 610-622, 2007.
D. H. Ausprunk and J. Folkman, "Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis, " Microvascular Research, vol. 14, no. 1, pp. 53-65, 1977.
D. W. Leung, G. Cachianes, W. J. Kuang, D. V. Goeddel, and N. Ferrara, "Vascular endothelial growth factor is a secreted angiogenic mitogen, " Science, vol. 246, no. 4935, pp. 1306-1309, 1989.
D. R. Senger, S. J. Galli, A. M. Dvorak, C. A. Perruzzi, V. S. Harvey, and H. F. Dvorak, "Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid, " Science, vol. 219, no. 4587, pp. 983-985, 1983.
S. Koch and L. Claesson-Welsh, "Signal transduction by vascular endothelial growth factor receptors, " Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 7, 2012.
L. Claesson-Welsh and M. Welsh, "VEGFA and tumour angiogenesis, " Journal of Internal Medicine, vol. 273, no. 2, pp. 114-127, 2013.
D. Hanahan and J. Folkman, "Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis, " Cell, vol. 86, no. 3, pp. 353-364, 1996.
R. Kerbel and J. Folkman, "Clinical translation of angiogenesis inhibitors, " Nature Reviews. Cancer, vol. 2, no. 10, pp. 727-739, 2002.
H. Wu, X. Zhang, D. Han, J. Cao, and J. Tian, "Tumour-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8, " PeerJ, vol. 8, article e8721, 2020.
W. Hansen, M. Hutzler, S. Abel et al., "Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth, " The Journal of Experimental Medicine, vol. 209, no. 11, pp. 2001-2016, 2012.
A. Shimizu, D. Zankov, M. Kurokawa-Seo, and H. Ogita, "Vascular endothelial growth factor-a exerts diverse cellular effects via small G proteins, Rho and Rap, " International Journal of Molecular Sciences, vol. 19, no. 4, p. 1203, 2018.
M. Shibuya, "Vascular endothelial growth factor and its receptor system: Physiological functions in angiogenesis and pathological roles in various diseases, " Journal of Biochemistry, vol. 153, no. 1, pp. 13-19, 2013.
S. J. Heasman and A. J. Ridley, "Mammalian Rho GTPases: New insights into their functions from in vivo studies, " Nature Reviews Molecular Cell Biology, vol. 9, no. 9, pp. 690-701, 2008.
M. Sopo, M. Anttila, K. Hämälaïnen et al., "Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer, " BMC Cancer, vol. 19, no. 1, p. 584, 2019.
Y. Z. Dang, Y. Zhang, J. P. Li et al., "High VEGFR1/2 expression levels are predictors of poor survival in patients with cervical cancer, " Medicine (Baltimore), vol. 96, no. 1, article e5772, 2017.
J. S. Wey, F. Fan, M. J. Gray et al., "Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines, " Cancer, vol. 104, no. 2, pp. 427-438, 2005.
R. Valtola, P. Salven, P. Heikkilä et al., "VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer, " The American Journal of Pathology, vol. 154, no. 5, pp. 1381-1390, 1999.
C. Tacconi, F. Ungaro, C. Correale et al., "Activation of the VEGFC/VEGFR3 pathway induces tumor immune escape in colorectal cancer, " Cancer Research, vol. 79, no. 16, pp. 4196-4210, 2019.
A. L. Elaimy and A. M. Mercurio, "Convergence of VEGF and YAP/TAZ signaling: Implications for angiogenesis and cancer biology, " Science Signaling, vol. 11, no. 552, article eaau1165, 2018.
S. Soker, M. Kaefer, M. Johnson, M. Klagsbrun, A. Atala, and M. R. Freeman, "Vascular endothelial growth factormediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype, " The American Journal of Pathology, vol. 159, no. 2, pp. 651-659, 2001.
S. Soker, S. Takashima, H. Q. Miao, G. Neufeld, and M. Klagsbrun, "Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor, " Cell, vol. 92, no. 6, pp. 735-745, 1998.
E. Geretti, A. Shimizu, and M. Klagsbrun, "Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis, " Angiogenesis, vol. 11, no. 1, pp. 31-39, 2008.
H. F. Guo and C. W. Vander Kooi, "Neuropilin functions as an essential cell surface receptor, " The Journal of Biological Chemistry, vol. 290, no. 49, pp. 29120-29126, 2015.
M. W. Parker, P. Xu, X. Li, and C. W. Vander Kooi, "Structural basis for selective vascular endothelial growth factor-A (VEGF-A) binding to neuropilin-1, " The Journal of Biological Chemistry, vol. 287, no. 14, pp. 11082-11089, 2012.
M. Rossignol, M. L. Gagnon, and M. Klagsbrun, "Genomic organization of human neuropilin-1 and neuropilin-2 genes: Identification and distribution of splice variants and soluble isoforms, " Genomics, vol. 70, no. 2, pp. 211-222, 2000.
H. Chen, A. Chédotal, Z. He, C. S. Goodman, and M. Tessier-Lavigne, "Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III, " Neuron, vol. 19, no. 3, pp. 547-559, 1997.
A. L. Kolodkin, D. V. Levengood, E. G. Rowe, Y. T. Tai, R. J. Giger, and D. D. Ginty, "Neuropilin is a semaphorin III receptor, " Cell, vol. 90, no. 4, pp. 753-762, 1997.
T. Takahashi, A. Fournier, F. Nakamura et al., "Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors, " Cell, vol. 99, no. 1, pp. 59-69, 1999.
M. L. Winberg, J. N. Noordermeer, L. Tamagnone et al., "Plexin A is a neuronal semaphorin receptor that controls axon guidance, " Cell, vol. 95, no. 7, pp. 903-916, 1998.
G. Neufeld, O. Kessler, and Y. Herzog, "The interaction of neuropilin-1 and neuropilin-2 with tyrosine-kinase receptors for VEGF, " Advances in Experimental Medicine and Biology, vol. 515, pp. 81-90, 2002.
H. Al-Koussa, O. El Atat, L. Jaafar, H. Tashjian, and M. El-Sibai, "The role of Rho GTPases in motility and invasion of glioblastoma cells, " Analytical Cellular Pathology (Amsterdam), vol. 2020, article 9274016, 9 pages, 2020.
K. Burridge and K. Wennerberg, "Rho and Rac take center stage, " Cell, vol. 116, no. 2, pp. 167-179, 2004.
A. J. Ridley, "Rho GTPase signalling in cell migration, " Current Opinion in Cell Biology, vol. 36, pp. 103-112, 2015.
S. Hanna and M. El-Sibai, "Signaling networks of Rho GTPases in cell motility, " Cellular Signalling, vol. 25, no. 10, pp. 1955-1961, 2013.
B. Boettner and L. Van Aelst, "The role of Rho GTPases in disease development, " Gene, vol. 286, no. 2, pp. 155-174, 2002.
A. Schmidt and A. Hall, "Guanine nucleotide exchange factors for Rho GTPases: Turning on the switch, " Genes & Development, vol. 16, no. 13, pp. 1587-1609, 2002.
D. A. Lauffenburger and A. F. Horwitz, "Cell migration: A physically integrated molecular process, " Cell, vol. 84, no. 3, pp. 359-369, 1996.
M. El-Sibai, P. Nalbant, H. Pang et al., "Cdc 42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells, " Journal of Cell Science, vol. 120, Part 19, pp. 3465-3474, 2007.
J. S. Condeelis, J. B. Wyckoff, M. Bailly et al., "Lamellipodia in invasion, " Seminars in Cancer Biology, vol. 11, no. 2, pp. 119-128, 2001.
K. Rottner, A. Hall, and J. V. Small, "Interplay between Rac and Rho in the control of substrate contact dynamics, " Current Biology, vol. 9, no. 12, pp. 640-648, 1999.
I. Kaverina, O. Krylyshkina, and J. V. Small, "Regulation of substrate adhesion dynamics during cell motility, " The International Journal of Biochemistry & Cell Biology, vol. 34, no. 7, pp. 746-761, 2002.
A. Garcia-Cattaneo and V. M. M. Braga, "Hold on tightly: How to keep the local activation of small GTPases, " Cell Adhesion & Migration, vol. 7, no. 3, pp. 283-287, 2013.
X. Trepat, Z. Chen, and K. Jacobson, "Cell migration, " Comprehensive Physiology, vol. 2, no. 4, pp. 2369-2392, 2012.
A. Y. Alexandrova, K. Arnold, S. Schaub et al., "Comparative dynamics of retrograde actin flow and focal adhesions: Formation of nascent adhesions triggers transition from fast to slow flow, " PLoS One, vol. 3, no. 9, article e3234, 2008.
L. Goldberg and Y. Kloog, "A Ras inhibitor tilts the balance between Rac and Rho and blocks phosphatidylinositol 3-kinase-dependent glioblastoma cell migration, " Cancer Research, vol. 66, no. 24, pp. 11709-11717, 2006.
J. T. Parsons, A. R. Horwitz, and M. A. Schwartz, "Cell adhesion: Integrating cytoskeletal dynamics and cellular tension, " Nature Reviews Molecular Cell Biology, vol. 11, no. 9, pp. 633-643, 2010.
T. J. Manning Jr., J. C. Parker, and H. Sontheimer, "Role of lysophosphatidic acid and rho in glioma cell motility, " Cell Motility and the Cytoskeleton, vol. 45, no. 3, pp. 185-199, 2000.
S. E. Hernández, J. Settleman, and A. J. Koleske, "Adhesiondependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase, " Current Biology, vol. 14, no. 8, pp. 691-696, 2004.
X. D. Ren, W. B. Kiosses, and M. A. Schwartz, "Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton, " The EMBO Journal, vol. 18, no. 3, pp. 578-585, 1999.
I. Abécassis, B. Olofsson, M. Schmid, G. Zalcman, and A. Karniguian, "RhoA induces MMP-9 expression at CD44 lamellipodial focal complexes and promotes HMEC-1 cell invasion, " Experimental Cell Research, vol. 291, no. 2, pp. 363-376, 2003.
S. Al-Dimassi, G. Salloum, B. Saykali et al., "Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion, " International Journal of Oncology, vol. 48, no. 5, pp. 1913-1920, 2016.
D. R. Croft and M. F. Olson, "Transcriptional regulation of Rho GTPase signaling, " Transcription, vol. 2, no. 5, pp. 211-215, 2011.
G. C. Prendergast, "Farnesyltransferase inhibitors define a role for RhoB in controlling neoplastic pathophysiology, " Histology and Histopathology, vol. 16, no. 1, pp. 269-275, 2001.
A. P. Wheeler and A. J. Ridley, "RhoB affects macrophage adhesion, integrin expression and migration, " Experimental Cell Research, vol. 313, no. 16, pp. 3505-3516, 2007.
M. A. Forget, R. R. Desrosiers, M. Del et al., "The expression of rho proteins decreases with human brain tumor progression: Potential tumor markers, " Clinical & Experimental Metastasis, vol. 19, no. 1, pp. 9-15, 2002.
F. M. Vega, A. Colomba, N. Reymond, M. Thomas, and A. J. Ridley, "RhoB regulates cell migration through altered focal adhesion dynamics, " Open Biology, vol. 2, no. 5, p. 120076, 2012.
A. Kwiatkowska, S. Didier, S. Fortin et al., "The small GTPase RhoG mediates glioblastoma cell invasion, " Molecular Cancer, vol. 11, no. 1, p. 65, 2012.
Z. D. Xu, T. Hao, and Y. H. Gan, "RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinoma cells, " Oral Diseases, vol. 26, no. 2, pp. 302-312, 2020.
H. Okura, B. J. Golbourn, U. Shahzad et al., "A role for activated Cdc42 in glioblastoma multiforme invasion, " Oncotarget, vol. 7, no. 35, pp. 56958-56975, 2016.
O. El Atat, A. Fakih, and M. El-Sibai, "RHOG activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells, " Cells, vol. 8, no. 2, p. 171, 2019.
S. Nicolas, S. Abdellatef, M. A. Haddad, I. Fakhoury, and M. el-Sibai, "Hypoxia and EGF stimulation regulate VEGF expression in human glioblastoma multiforme (GBM) cells by differential regulation of the PI3K/Rho-GTPase and MAPK pathways, " Cells, vol. 8, no. 11, article 1397, 2019.
Z. H. Zhao, Y. Tian, J. P. Yang, J. Zhou, and K. S. Chen, "RhoC, vascular endothelial growth factor and microvascular density in esophageal squamous cell carcinoma, " World Journal of Gastroenterology, vol. 21, no. 3, pp. 905-912, 2015.
W.-F. Gou, Y. Zhao, H. Lu et al., "The role of RhoC in epithelial-to-mesenchymal transition of ovarian carcinoma cells, " BMC Cancer, vol. 14, no. 1, p. 477, 2014.
T. Kamai, T. Tsujii, K. Arai et al., "Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer, " Clinical Cancer Research, vol. 9, no. 7, pp. 2632-2641, 2003.
A. Eriksson, R. Cao, J. Roy et al., "Small GTP-binding protein Rac is an essential mediator of vascular endothelial growth factor-induced endothelial fenestrations and vascular permeability, " Circulation, vol. 107, no. 11, pp. 1532-1538, 2003.
M. Yamaoka-Tojo, M. Ushio-Fukai, L. Hilenski et al., "IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation, " Circulation Research, vol. 95, no. 3, pp. 276-283, 2004.
D. Yamazaki, S. Suetsugu, H. Miki et al., "WAVE2 is required for directed cell migration and cardiovascular development, " Nature, vol. 424, no. 6947, pp. 452-456, 2003.
L. Lamalice, F. Houle, G. Jourdan, and J. Huot, "Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGFinduced activation of Cdc42 upstream of SAPK2/p38, " Oncogene, vol. 23, no. 2, pp. 434-445, 2004.
H. Sun, J. W. Breslin, J. Zhu, S. Y. Yuan, and M. H. Wu, "Rho and ROCK signaling in VEGF-induced microvascular endothelial hyperpermeability, " Microcirculation, vol. 13, no. 3, pp. 237-247, 2006.
E. Dejana, "Endothelial cell-cell junctions: Happy together, " Nature Reviews Molecular Cell Biology, vol. 5, no. 4, pp. 261-270, 2004.
M. V. Hoang, M. C. Whelan, and D. R. Senger, "Rho activity critically and selectively regulates endothelial cell organization during angiogenesis, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 1874-1879, 2004.
G. Gadea, V. Sanz-Moreno, A. Self, A. Godi, and C. J. Marshall, "DOCK10-mediated Cdc42 activation is necessary for amoeboid invasion of melanoma cells, " Current Biology, vol. 18, no. 19, pp. 1456-1465, 2008.
V. Sanz-Moreno, G. Gadea, J. Ahn et al., "Rac activation and inactivation control plasticity of tumor cell movement, " Cell, vol. 135, no. 3, pp. 510-523, 2008.
M. T. Bolinger and D. A. Antonetti, "Moving past anti-VEGF: Novel therapies for treating diabetic retinopathy, " International Journal of Molecular Sciences, vol. 17, no. 9, article 1498, 2016.
M. Yamaguchi, S. Nakao, M. Arima et al., "Rho-kinase/ROCK as a potential drug target for vitreoretinal diseases, " Journal of Ophthalmology, vol. 2017, Article ID 8543592, 8 pages, 2017.
S. Chen, J. Wang, W. F. Gou et al., "The involvement of RhoA and Wnt-5a in the tumorigenesis and progression of ovarian epithelial carcinoma, " International Journal of Molecular Sciences, vol. 14, no. 12, pp. 24187-24199, 2013.
F. Fan, J. S. Wey, M. F. McCarty et al., "Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells, " Oncogene, vol. 24, no. 16, pp. 2647-2653, 2005.
M. Inoue, J. H. Hager, N. Ferrara, H. P. Gerber, and D. Hanahan, "VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic beta cell carcinogenesis, " Cancer Cell, vol. 1, no. 2, pp. 193-202, 2002.
I. Mirones, C. J. Conti, J. Martínez, M. Garcia, and F. Larcher, "Complexity of VEGF responses in skin carcinogenesis revealed through ex vivo assays based on a VEGF-A null mouse keratinocyte cell line, " The Journal of Investigative Dermatology, vol. 129, no. 3, pp. 730-741, 2009.
S. T. Park, B. R. Kim, S. H. Park et al., "Suppression of VEGF expression through interruption of the HIF-1 and Akt signaling cascade modulates the anti-angiogenic activity of DAPK in ovarian carcinoma cells, " Oncology Reports, vol. 31, no. 2, pp. 1021-1029, 2014.
Y. Xue, F. Bi, X. Zhang et al., "Role of Rac1 and Cdc42 in hypoxia induced p53 and von Hippel-Lindau suppression and HIF1alpha activation, " International Journal of Cancer, vol. 118, no. 12, pp. 2965-2972, 2006.
R. C. Bates, J. D. Goldsmith, R. E. Bachelder et al., "Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids, " Current Biology, vol. 13, no. 19, pp. 1721-1727, 2003.
J. L. Su, P. C. Yang, J. Y. Shih et al., "The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells, " Cancer Cell, vol. 9, no. 3, pp. 209-223, 2006.
R. Aesoy, B. C. Sanchez, J. H. Norum, R. Lewensohn, K. Viktorsson, and B. Linderholm, "An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells, " Molecular Cancer Research, vol. 6, no. 10, pp. 1630-1638, 2008.
S. Oommen, S. K. Gupta, and N. E. Vlahakis, "Vascular endothelial growth factor A (VEGF-A) induces endothelial and cancer cell migration through direct binding to integrin {alpha}9{beta}1: Identification of a specific {alpha}9{beta}1 binding site, " The Journal of Biological Chemistry, vol. 286, no. 2, pp. 1083-1092, 2011.
Q. D. Nguyen, S. Rodrigues, C. M. Rodrigue et al., "Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts, " Molecular Cancer Therapeutics, vol. 5, no. 8, pp. 2070-2077, 2006.
A. Shimizu, A. Mammoto, J. E. Italiano Jr. et al., "ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells, " The Journal of Biological Chemistry, vol. 283, no. 40, pp. 27230-27238, 2008.
Y. Cao, G. E, E. Wang et al., "VEGF exerts an angiogenesisindependent function in cancer cells to promote their malignant progression, " Cancer Research, vol. 72, no. 16, pp. 3912-3918, 2012.
J. S. Wey, M. J. Gray, F. Fan et al., "Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells, " British Journal of Cancer, vol. 93, no. 2, pp. 233-241, 2005.
M. Snuderl, A. Batista, N. D. Kirkpatrick et al., "Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma, " Cell, vol. 152, no. 5, pp. 1065-1076, 2013.
A. Yoshida, A. Shimizu, H. Asano et al., "VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells, " Biology Open, vol. 4, no. 9, pp. 1063-1076, 2015.
T. W. Chittenden, J. Pak, R. Rubio et al., "Therapeutic implications of GIPC1 silencing in cancer, " PLoS One, vol. 5, no. 12, article e15581, 2010.
D. Wu, A. Haruta, and Q. Wei, "GIPC1 interacts with Myo-GEF and promotes MDA-MB-231 breast cancer cell invasion, " The Journal of Biological Chemistry, vol. 285, no. 37, pp. 28643-28650, 2010.
R. Hernández-Garciá, M. L. Iruela-Arispe, G. Reyes-Cruz, and J. Vázquez-Prado, "Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells, " Vascular Pharmacology, vol. 74, pp. 60-72, 2015.
S. Lamouille, J. Xu, and R. Derynck, "Molecular mechanisms of epithelial-mesenchymal transition, " Nature Reviews. Molecular Cell Biology, vol. 15, no. 3, pp. 178-196, 2014.
T. J. Abou-Antoun, J. Nazarian, A. Ghanem, S. Vukmanovic, and A. D. Sandler, "Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance, " PLoS One, vol. 13, no. 1, article e0189711, 2018.
M. Al Hassan, I. Fakhoury, Z. El Masri et al., "Metformin treatment inhibits motility and invasion of glioblastoma cancer cells, " Analytical Cellular Pathology (Amsterdam), vol. 2018, article 5917470, 9 pages, 2018.
J. El-Amm and J. B. Aragon-Ching, "Targeting bone metastases in metastatic castration-resistant prostate cancer, " Clinical Medicine Insights: Oncology, vol. 10, Supplement 1, pp. 11-19, 2016.
R. Nader, J. El Amm, and J. B. Aragon-Ching, "Role of chemotherapy in prostate cancer, " Asian Journal of Andrology, vol. 20, no. 3, pp. 221-229, 2018.
G. Nasreddine, M. El-Sibai, and R. J. Abi-Habib, "Cytotoxicity of [HuArgI (co)-PEG 5000]-induced arginine deprivation to ovarian cancer cells is autophagy dependent, " Investigational New Drugs, vol. 38, no. 1, pp. 10-19, 2020.