Characterization of Class-3 Semaphorin Receptors, Neuropilins and Plexins, as Therapeutic Targets in a Pan-Cancer Study
Abstract
:1. Introduction
2. Results
2.1. Neuropilins and Plexins Are Dysregulated in Primary Tumors and with Further Dysregulation in Metatstatic Tumors
2.2. Expression of Neuropilins and Plexins Are Associated with Semaphroin Key Transducers
2.3. Expression of Neuropilins and Plexins Are Associated with Patient Survival
2.4. Neuropilins and Plexins Are Associated with Immune Infiltration Subtypes and Tumor Microenvironment in Cancer
2.5. Neuropilins and Plexins Are Associated with Tumor Stemness and Cancer Cell Response to Chemotherapy
2.6. Neuropilins and Plexins in Breast Cancer
2.6.1. Neuropilins and Plexins Are Dysregulated in Breast Cancer and Their Expression Is Tumor Subtype Specific
2.6.2. Neuropilins and Plexins Are Associated with Tumor Microenvironment and Patient Survival in Breast Cancer
3. Discussion
4. Methods
4.1. Datasets Used
4.2. Tumor Microenvironment Analyses
4.3. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
SEMA3 | class-3 semaphorins |
NRPs | Neuropilins |
PLXN | Plexins |
TCGA | the cancer genome atlas |
RNAss | tumor cell stemness based on mRNA expression |
DNAss | tumor stemness based on DNA methylation |
r | correlation coefficient |
ANOVA | analysis of variance |
For the cancer type abbreviations (TCGAID) please refer to Table S1 |
References
- Feiner, L.; Koppel, A.M.; Kobayashi, H.; Raper, J.A. Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron 1997, 19, 539–545. [Google Scholar] [CrossRef] [Green Version]
- Angelopoulou, E.; Piperi, C. Emerging role of plexins signaling in glioma progression and therapy. Cancer Lett. 2018, 414, 81–87. [Google Scholar] [CrossRef]
- Worzfeld, T.; Offermanns, S. Semaphorins and plexins as therapeutic targets. Nat. Rev. Drug Discov. 2014, 13, 603–621. [Google Scholar] [CrossRef] [PubMed]
- Kumanogoh, A.; Kikutani, H. Immunological functions of the neuropilins and plexins as receptors for semaphorins. Nat. Rev. Immunol. 2013, 13, 802–814. [Google Scholar] [CrossRef] [PubMed]
- Capparuccia, L.; Tamagnone, L. Semaphorin signaling in cancer cells and in cells of the tumor microenvironment—Two sides of a coin. J. Cell Sci. 2009, 122 Pt 11, 1723–1736. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, K.; Kumanogoh, A.; Kikutani, H. Semaphorins and their receptors in immune cell interactions. Nat. Immunol. 2008, 9, 17–23. [Google Scholar] [CrossRef] [PubMed]
- Tamagnone, L. Emerging role of semaphorins as major regulatory signals and potential therapeutic targets in cancer. Cancer Cell 2012, 22, 145–152. [Google Scholar] [CrossRef] [Green Version]
- Toledano, S.; Nir-Zvi, I.; Engelman, R.; Kessler, O.; Neufeld, G. Class-3 semaphorins and their receptors: Potent multifunctional modulators of tumor progression. Int. J. Mol. Sci. 2019, 20, 556. [Google Scholar] [CrossRef] [Green Version]
- Takahashi, T.; Fournier, A.; Nakamura, F.; Wang, L.H.; Murakami, Y.; Kalb, R.G.; Fujisawa, H.; Strittmatter, S.M. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 1999, 99, 59–69. [Google Scholar] [CrossRef] [Green Version]
- Tamagnone, L.; Artigiani, S.; Chen, H.; He, Z.; Ming, G.-L.; Song, H.-J.; Chédotal, A.; Winberg, M.L.; Goodman, C.S.; Poo, M.-M.; et al. Plexins are a large family of receptors for transmembrane, secreted, and gpi-anchored semaphorins in vertebrates. Cell 1999, 99, 71–80. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.; Klamer, B.; Li, J.; Fernandez, S.; Li, L. A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer. BMC Med. Genom. 2020, 13 (Suppl. 5), 45. [Google Scholar] [CrossRef] [PubMed]
- Nasarre, P.; Gemmill, R.M.; Drabkin, H.A. The emerging role of class-3 semaphorins and their neuropilin receptors in oncology. OncoTargets Ther. 2014, 7, 1663–1687. [Google Scholar]
- Neufeld, G.; Mumblat, Y.; Smolkin, T.; Toledano, S.; Nir-Zvi, I.; Ziv, K.; Kessler, O. The semaphorins and their receptors as modulators of tumor progression. Drug Resist. Updates 2016, 29, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Roy, S.; Bag, A.K.; Singh, R.K.; Talmadge, J.E.; Batra, S.K.; Datta, K. Multifaceted role of neuropilins in the immune system: Potential targets for immunotherapy. Front. Immunol. 2017, 8, 1228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bagri, A.; Tessier-Lavigne, M.; Watts, R.J. Neuropilins in tumor biology. Clin. Cancer Res. 2009, 15, 1860–1864. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bielenberg, D.R.; Pettaway, C.A.; Takashima, S.; Klagsbrun, M. Neuropilins in neoplasms: Expression, regulation, and function. Exp. Cell Res. 2006, 312, 584–593. [Google Scholar] [CrossRef]
- Chaudhary, B.; Khaled, Y.; Ammori, B.J.; Elkord, E. Neuropilin 1: Function and therapeutic potential in cancer. Cancer Immunol. Immunother. 2014, 63, 81–99. [Google Scholar] [CrossRef]
- Prud’Homme, G.J.; Glinka, Y. Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity. Oncotarget 2012, 3, 921–939. [Google Scholar] [CrossRef] [Green Version]
- Maione, F.; Molla, F.; Meda, C.; Latini, R.; Zentilin, L.; Giacca, M.; Seano, G.; Serini, G.G.; Bussolino, F.; Giraudo, E. Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models. J. Clin. Investig. 2009, 119, 3356–3372. [Google Scholar] [CrossRef]
- Wong, H.K.; Shimizu, A.; Kirkpatrick, N.D.; Garkavtsev, I.; Chan, A.W.; Tamaso, E.d.; Klagsbrun, M.; Jain, R.K. Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism. Neoplasia 2012, 14, 84–94. [Google Scholar] [CrossRef] [Green Version]
- Niland, S.; Eble, J.A. Neuropilin: Handyman and power broker in the tumor microenvironment. Adv. Exp. Med. Biol. 2020, 1223, 31–67. [Google Scholar] [PubMed]
- Hota, P.K.; Buck, M. Plexin structures are coming: Opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions. Cell. Mol. Life Sci. 2012, 69, 3765–3805. [Google Scholar] [CrossRef] [PubMed]
- Gitler, A.D.; Lu, M.M.; Epstein, J.A. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev. Cell 2004, 7, 107–116. [Google Scholar] [CrossRef] [Green Version]
- Peacock, J.W.; Takeuchi, A.; Hayashi, N.; Liu, L.; Tam, K.J.; Al Nakouzi, N.; Khazamipour, N.; Tombe, T.; Dejima, T.; Lee, K.C.; et al. SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1. EMBO Mol. Med. 2018, 10, 219–238. [Google Scholar] [CrossRef]
- Ben-Zvi, A.; Manor, O.; Schachner, M.; Yaron, A.; Tessier-Lavigne, M.; Behar, O. The semaphorin receptor PlexinA3 mediates neuronal apoptosis during dorsal root ganglia development. J. Neurosci. 2008, 28, 12427–12432. [Google Scholar] [CrossRef] [Green Version]
- Kigel, B.; Rabinowicz, N.; Varshavsky, A.; Kessler, O.; Neufeld, G. Plexin-A4 promotes tumor progression and tumor angiogenesis by enhancement of VEGF and bFGF signaling. Blood 2011, 118, 4285–4296. [Google Scholar] [CrossRef]
- Sabag, A.D.; Smolkin, T.; Mumblat, Y.; Ueffing, M.; Kessler, O.; Gloeckner, C.J.; Neufeld, G. The role of the plexin-A2 receptor in Sema3A and Sema3B signal transduction. J. Cell Sci. 2014, 127 Pt 24, 5240–5252. [Google Scholar] [CrossRef] [Green Version]
- Gu, C. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 2005, 307, 265–268. [Google Scholar] [CrossRef]
- Hamm, M.J.; Kirchmaier, B.C.; Herzog, W. Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1. J. Cell Biol. 2016, 215, 415–430. [Google Scholar] [CrossRef] [Green Version]
- Liu, X.; Uemura, A.; Fukushima, Y.; Yoshida, Y.; Hirashima, M. Semaphorin 3G provides a repulsive guidance cue to lymphatic endothelial cells via Neuropilin-2/PlexinD1. Cell Rep. 2016, 17, 2299–2311. [Google Scholar] [CrossRef] [Green Version]
- Smolkin, T.; Nir-Zvi, I.; Duvshani, N.; Mumblat, Y.; Kessler, O.; Neufeld, G. Complexes of plexin-A4 and plexin-D1 convey semaphorin-3C signals to induce cytoskeletal collapse in the absence of neuropilins. J. Cell Sci. 2018, 131, jcs208298. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aghajanian, H.; Choi, C.; Ho, V.C.; Gupta, M.; Singh, M.K.; Epstein, J.A. Semaphorin 3d and semaphorin 3e direct endothelial motility through distinct molecular signaling pathways. J. Biol. Chem. 2014, 289, 17971–17979. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharma, A.; Verhaagen, J.; Harvey, A.R. Receptor complexes for each of the Class 3 Semaphorins. Front. Cell. Neurosci. 2012, 6, 28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, H.; Vreeken, D.; Junaid, A.; Wang, G.; Sol, W.M.; De Bruin, R.G.; Van Zonneveld, A.J.; Van Gils, J.M. Endothelial semaphorin 3F maintains endothelial barrier function and inhibits monocyte migration. Int. J. Mol. Sci. 2020, 21, 1471. [Google Scholar] [CrossRef] [Green Version]
- Franco, M.; Tamagnone, L. Tyrosine phosphorylation in semaphorin signalling: Shifting into overdrive. EMBO Rep. 2008, 9, 865–871. [Google Scholar] [CrossRef]
- Oinuma, I.; Ishikiwa, Y.; Katoh, H.; Negishi, M. The semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 2004, 305, 862–865. [Google Scholar] [CrossRef]
- Rohm, B.; Rahim, B.; Kleiber, B.; Hovatta, I.; Püschel, A.W. The semaphorin 3A receptor may directly regulate the activity of small GTPases. FEBS Lett. 2000, 486, 68–72. [Google Scholar] [CrossRef]
- Tong, Y.; Chugha, P.; Hota, P.K.; Alviani, R.S.; Li, M.; Tempel, W.; Shen, L.; Park, H.-W.; Buck, M. Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain. J. Biol. Chem. 2007, 282, 37215–37224. [Google Scholar] [CrossRef] [Green Version]
- Mertins, P.; Cptac, N.; Mani, D.R.; Ruggles, K.; Gillette, M.A.; Clauser, K.R.; Wang, P.; Wang, X.; Qiao, J.W.; Cao, S.; et al. Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 2016, 534, 55–62. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Liu, T.; Zhang, Z.; Payne, S.H.; Zhang, B.; E McDermott, J.; Zhou, J.-Y.; Petyuk, V.A.; Chen, L.; Ray, D.; et al. Integrated proteogenomic characterization of human high-grade serous ovarian cancer. Cell 2016, 166, 755–765. [Google Scholar] [CrossRef] [Green Version]
- Zhang, B.; Cptac, T.N.; Wang, J.; Wang, X.; Zhu, J.; Liu, Q.; Shi, Z.; Chambers, M.C.; Zimmerman, L.J.; Shaddox, K.F.; et al. Proteogenomic characterization of human colon and rectal cancer. Nature 2014, 513, 382–387. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takamatsu, H.; Okuno, T.; Kumanogoh, A. Regulation of immune cell responses by semaphorins and their receptors. Cell. Mol. Immunol. 2010, 7, 83–88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Franzolin, G.; Tamagnone, L. Semaphorin signaling in cancer-associated inflammation. Int. J. Mol. Sci. 2019, 20, 377. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alamri, A.; Rahman, R.; Zhang, M.; Alamri, A.; Gounni, A.S.; Kung, S.K. Semaphorin-3E produced by immature dendritic cells regulates activated natural killer cells migration. Front. Immunol. 2018, 9, 1005. [Google Scholar] [CrossRef] [Green Version]
- Alfaro, D.; García-Ceca, J.; Cejalvo, T.; Jimenez, E.; Jenkinson, E.J.; Anderson, G.; Muñoz, J.J.; Zapata, A.G. EphrinB1-EphB signaling regulates thymocyte-epithelium interactions involved in functional T cell development. Eur. J. Immunol. 2007, 37, 2596–2605. [Google Scholar] [CrossRef] [PubMed]
- Roney, K.; Holl, E.; Ting, J. Immune plexins and semaphorins: Old proteins, new immune functions. Protein Cell 2013, 4, 17–26. [Google Scholar] [CrossRef] [Green Version]
- Takamatsu, H.; Takegahara, N.; Nakagawa, Y.; Tomura, M.; Taniguchi, M.; Friedel, R.H.; Rayburn, H.; Tessier-Lavigne, M.; Yoshida, Y.; Okuno, T.; et al. Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat. Immunol. 2010, 11, 594–600. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takegahara, N.; Takamatsu, H.; Toyofuku, T.; Tsujimura, T.; Okuno, T.; Yukawa, K.; Mizui, M.; Yamamoto, M.; Prasad, D.V.; Suzuki, K.; et al. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat. Cell Biol. 2006, 8, 615–622. [Google Scholar] [CrossRef] [PubMed]
- Holl, E.K.; O’Connor, B.P.; Holl, T.M.; Roney, K.E.; Zimmermann, A.G.; Jha, S.; Kelsoe, G.; Ting, J.P.-Y. Plexin-D1 is a novel regulator of germinal centers and humoral immune responses. J. Immunol. 2011, 186, 5603–5611. [Google Scholar] [CrossRef] [Green Version]
- Thorsson, V.; Gibbs, D.L.; Brown, S.; Wolf, D.; Bortone, D.S.; Yang, T.-H.O.; Porta-Pardo, E.; Gao, G.F.; Plaisier, C.L.; Eddy, J.A.; et al. The immune landscape of cancer. Immunity 2018, 48, 812–830.e14. [Google Scholar] [CrossRef] [Green Version]
- Becht, E.; Giraldo, N.A.; Lacroix, L.; Buttard, B.; Elarouci, N.; Petitprez, F.; Selves, J.; Laurent-Puig, P.; Sautès-Fridman, C.; Fridman, W.H.; et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016, 17, 218. [Google Scholar] [CrossRef] [PubMed]
- Yoshihara, K.; Shahmoradgoli, M.; Martinez, E.; Vegesna, R.; Kim, H.; Torres-García, W.; Treviño, V.; Shen, H.; Laird, P.W.; Levine, U.A.; et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 2013, 4, 2612. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Endres, S.; Kobold, S. Enhancing tumor T cell infiltration to enable cancer immunotherapy. Immunotherapy 2019, 11, 201–213. [Google Scholar] [CrossRef]
- Atashzar, M.R.; Baharlou, R.; Karami, J.; Abdollahi, H.; Rezaei, R.; Pourramezan, F.; Moghaddam, S.H.Z. Cancer stem cells: A review from origin to therapeutic implications. J. Cell. Physiol. 2020, 235, 790–803. [Google Scholar] [CrossRef] [PubMed]
- Maione, F.; Capano, S.; Regano, D.; Zentilin, L.; Giacca, M.; Casanovas, O.; Bussolino, F.; Serini, G.G.; Giraudo, E. Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by antiangiogenic treatment in mice. J. Clin. Investig. 2012, 122, 1832–1848. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hao, J.; Yu, J.S. Semaphorin 3C and its receptors in cancer and cancer stem-like cells. Biomedicines 2018, 6, 42. [Google Scholar] [CrossRef] [Green Version]
- Man, J.; Shoemake, J.; Zhou, W.; Fang, X.; Wu, Q.; Rizzo, A.; Prayson, R.; Bao, S.; Rich, J.N.; Yu, J.S. Sema3C promotes the survival and tumorigenicity of glioma stem cells through Rac1 activation. Cell Rep. 2014, 9, 1812–1826. [Google Scholar] [CrossRef] [Green Version]
- Malta, T.M.; Sokolov, A.; Gentles, A.J.; Burzykowski, T.; Poisson, L.; Kaminska, B.; Huelsken, J.; Gevaert, O.; Colaprico, A.; Czerwińska, P.; et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell 2018, 173, 338–354.e15. [Google Scholar] [CrossRef] [Green Version]
- Izycka, N.; Sterzynska, K.; Januchowski, R.; Nowak-Markwitz, E. Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer—Review of literature. Ginekol. Pol. 2019, 90, 223–227. [Google Scholar] [CrossRef]
- Rizzolio, S.; Battistini, C.; Cagnoni, G.; Apicella, M.; Vella, V.; Giordano, S.; Tamagnone, L. Downregulating neuropilin-2 triggers a novel mechanism enabling EGFR-dependent resistance to oncogene-targeted therapies. Cancer Res. 2018, 78, 1058–1068. [Google Scholar] [CrossRef] [Green Version]
- Rizzolio, S.; Cagnoni, G.; Battistini, C.; Bonelli, S.; Isella, C.; A Van Ginderachter, J.; Bernards, R.; Di Nicolantonio, F.; Giordano, S.; Tamagnone, L. Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies. J. Clin. Investig. 2018, 128, 3976–3990. [Google Scholar] [CrossRef] [PubMed]
- Reinhold, W.C.; Sunshine, M.; Liu, H.; Varma, S.; Kohn, K.W.; Morris, J.; Doroshow, J.; Pommier, Y. CellMiner: A web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set. Cancer Res. 2012, 72, 3499–3511. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Butti, R.; Kumar, T.V.; Nimma, R.; Kundu, G.C. Impact of semaphorin expression on prognostic characteristics in breast cancer. Breast Cancer Targets Ther. 2018, 10, 79–88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neufeld, G.; Kessler, O. The semaphorins: Versatile regulators of tumour progression and tumour angiogenesis. Nat. Rev. Cancer 2008, 8, 632–645. [Google Scholar] [CrossRef] [PubMed]
- Shahi, P.; Wang, C.-Y.; Chou, J.; Hagerling, C.; Velozo, H.G.; Ruderisch, A.; Yu, Y.; Lai, M.-D.; Werb, Z. GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis. Oncogene 2017, 36, 5567–5575. [Google Scholar] [CrossRef] [Green Version]
- Pan, H.; Wanami, L.S.; Dissanayake, T.R.; Bachelder, R.E. Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells. Breast Cancer Res. Treat. 2009, 118, 197–205. [Google Scholar] [CrossRef] [Green Version]
- Zhu, X.; Zhang, X.; Ye, Z.; Chen, Y.; Lv, L.; Zhang, X.; Hu, H. Silencing of semaphorin 3C suppresses cell proliferation and migration in MCF-7 breast cancer cells. Oncol. Lett. 2017, 14, 5913–5917. [Google Scholar] [CrossRef] [Green Version]
- Malik, M.F.; Satherley, L.; Davies, E.L.; Ye, L.; Jiang, W.G. Expression of semaphorin 3C in breast cancer and its impact on adhesion and invasion of breast cancer cells. Anticancer Res. 2016, 36, 1281–1286. [Google Scholar]
- Mumblat, Y.; Kessler, O.; Ilan, N.; Neufeld, G. Full-length semaphorin-3C is an inhibitor of tumor lymphangiogenesis and metastasis. Cancer Res. 2015, 75, 2177–2186. [Google Scholar] [CrossRef] [Green Version]
- Xiong, G.; Wang, C.; Mark Evers, B.; Zhou, B.P.; Xu, R. RORalpha suppresses breast tumor invasion by inducing SEMA3F expression. Cancer Res. 2012, 72, 1728–1739. [Google Scholar] [CrossRef] [Green Version]
- Christensen, C.; Ambartsumian, N.; Gilestro, G.; Thomsen, B.; Comoglio, P.; Tamagnone, L.; Guldberg, P.; Lukanidin, E. Proteolytic processing converts the repelling signal Sema3E into an inducer of invasive growth and lung metastasis. Cancer Res. 2005, 65, 6167–6177. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nasarre, P.; Constantin, B.; Rouhaud, L.; Harnois, T.; Raymond, G.; Drabkin, H.A.; Bourmeyster, N.; Roche, J. Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. Neoplasia 2003, 5, 83–92. [Google Scholar] [CrossRef] [Green Version]
- Tamagnone, L.; Rehman, M. To die or not to die: Sema3E rules the game. Cancer Cell 2013, 24, 564–566. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Luchino, J.; Hocine, M.; Amoureux, M.-C.; Gibert, B.; Bernet, A.; Royet, A.; Treilleux, I.; Lécine, P.; Borg, J.P.; Mehlen, P.; et al. Semaphorin 3E suppresses tumor cell death triggered by the Plexin D1 dependence receptor in metastatic breast cancers. Cancer Cell 2013, 24, 673–685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Casazza, A.; Finisguerra, V.; Capparuccia, L.; Camperi, A.; Swiercz, J.M.; Rizzolio, S.; Rolny, C.; Christensen, C.; Bertotti, A.; Sarotto, I.; et al. Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice. J. Clin. Investig. 2010, 120, 2684–2698. [Google Scholar] [CrossRef] [Green Version]
- Chakraborty, G.; Kumar, S.; Mishra, R.; Patil, T.V.; Kundu, G.C. Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model. PLoS ONE 2012, 7, e33633. [Google Scholar] [CrossRef]
- Jurcak, N.R.; Rucki, A.A.; Muth, S.; Thompson, E.; Sharma, R.; Ding, D.; Zhu, Q.; Eshleman, J.R.; Anders, R.A.; Jaffee, E.M.; et al. Axon guidance molecules promote perineural invasion and metastasis of orthotopic pancreatic tumors in mice. Gastroenterology 2019, 157, 838–850.e6. [Google Scholar] [CrossRef]
- Ni, Q.; Sun, J.; Ma, C.; Li, Y.; Ju, J.; Sun, M. The neuropilins and their ligands in hematogenous metastasis of salivary adenoid cystic carcinoma—An immunohistochemical study. J. Oral Maxillofac. Surg. 2018, 76, 569–579. [Google Scholar] [CrossRef] [Green Version]
- Schonberg, D.L.; Lubelski, D.; E Miller, T.; Rich, J.N. Brain tumor stem cells: Molecular characteristics and their impact on therapy. Mol. Asp. Med. 2014, 39, 82–101. [Google Scholar] [CrossRef] [Green Version]
- Huang, Z.; Cheng, L.; Guryanova, O.A.; Wu, Q.; Bao, S. Cancer stem cells in glioblastoma—Molecular signaling and therapeutic targeting. Protein Cell 2010, 1, 638–655. [Google Scholar] [CrossRef]
- Bao, S.; Wu, Q.; McLendon, R.E.; Hao, Y.; Shi, Q.; Hjelmeland, A.B.; Dewhirst, M.W.; Bigner, D.D.; Rich, J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444, 756–760. [Google Scholar] [CrossRef] [PubMed]
- Ben, Q.; Zheng, J.; Fei, J.; An, W.; Li, P.; Li, Z.; Yuan, Y. High Neuropilin 1 expression was associated with angiogenesis and poor overall survival in resected pancreatic ductal adenocarcinoma. Pancreas 2014, 43, 744–749. [Google Scholar] [CrossRef] [PubMed]
- Handa, A.; Tokunaga, T.; Tsuchida, T.; Lee, Y.H.; Kijima, H.; Yamazaki, H.; Ueyama, Y.; Fukuda, H.; Nakamura, M. Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma. Int. J. Oncol. 2000, 17, 291–295. [Google Scholar] [CrossRef] [PubMed]
- Kawakami, T.; Tokunaga, T.; Hatanaka, H.; Kijima, H.; Yamazaki, H.; Abe, Y.; Osamura, Y.; Inoue, H.; Ueyama, Y.; Nakamura, M. Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer 2002, 95, 2196–2201. [Google Scholar] [CrossRef]
- Osada, H.; Tokunaga, T.; Nishi, M.; Hatanaka, H.; Abe, Y.; Tsugu, A.; Kijima, H.; Yamazaki, H.; Ueyama, Y.; Nakamura, M. Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in human glioma. Anticancer Res. 2004, 24, 547–552. [Google Scholar]
- Stephenson, J.M.; Banerjee, S.K.; Saxena, N.K.; Cherian, R.; Banerjee, S.K. Neuropilin-1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: A possible marker for the progression of breast cancer. Int. J. Cancer 2002, 101, 409–414. [Google Scholar] [CrossRef]
- Delloye-Bourgeois, C.; Jacquier, A.; Charoy, C.; Reynaud, F.; Nawabi, H.; Thoinet, K.; Kindbeiter, K.; Yoshida, Y.; Zagar, Y.; Kong, Y.; et al. PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments. Nat. Neurosci. 2015, 18, 36–45. [Google Scholar] [CrossRef]
- Lu, Y.; Xu, Q.; Zuo, Y.; Liu, L.; Liu, S.; Chen, L.; Wang, K.; Lei, Y.; Zhao, X.; Li, Y. Isoprenaline/beta2-AR activates Plexin-A1/VEGFR2 signals via VEGF secretion in gastric cancer cells to promote tumor angiogenesis. BMC Cancer 2017, 17, 875. [Google Scholar] [CrossRef] [Green Version]
- Nasarre, C.; Koncina, E.; Labourdette, G.; Cremel, G.; Roussel, G.; Aunis, M.; Bagnard, D. Neuropilin-2 acts as a modulator of Sema3A-dependent glioma cell migration. Cell Adhes. Migr. 2009, 3, 383–389. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.-Y.; Chen, L.; Li, Y.-H.; Xu, Q. PlexinA1 expression in gastric carcinoma and its relationship with tumor angiogenesis and proliferation. World J. Gastroenterol. 2007, 13, 6558–6561. [Google Scholar] [CrossRef] [Green Version]
- Presta, I.; Donato, A.; Malara, N.; Russo, E.; Hribal, M.L.; Donato, G. Classical differentiation protocols upregulate the expression of the axon guidance genes PLXNA2 and SEMA3C in SH-SY5Y neuroblastoma cells. Hum. Cell 2019, 32, 397–400. [Google Scholar] [CrossRef] [PubMed]
- Carretero-Ortega, J.; Chhangawala, Z.; Hunt, S.; Narvaez, C.; Menéndez-González, J.; Gay, C.M.; Zygmunt, T.; Li, X.; Torres-Vázquez, J. GIPC proteins negatively modulate Plexind1 signaling during vascular development. eLife 2019, 8, 8. [Google Scholar] [CrossRef] [PubMed]
- Choi, Y.I.; Duke-Cohan, J.S.; Chen, W.; Liu, B.; Rossy, J.; Tabarin, T.; Ju, L.; Gui, J.; Gaus, K.; Zhu, C.; et al. Dynamic control of beta1 integrin adhesion by the plexinD1-sema3E axis. Proc. Natl. Acad. Sci. USA 2014, 111, 379–384. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Team, R.C. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2018. [Google Scholar]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, X.; Shao, S.; Li, L. Characterization of Class-3 Semaphorin Receptors, Neuropilins and Plexins, as Therapeutic Targets in a Pan-Cancer Study. Cancers 2020, 12, 1816. https://doi.org/10.3390/cancers12071816
Zhang X, Shao S, Li L. Characterization of Class-3 Semaphorin Receptors, Neuropilins and Plexins, as Therapeutic Targets in a Pan-Cancer Study. Cancers. 2020; 12(7):1816. https://doi.org/10.3390/cancers12071816
Chicago/Turabian StyleZhang, Xiaoli, Shuai Shao, and Lang Li. 2020. "Characterization of Class-3 Semaphorin Receptors, Neuropilins and Plexins, as Therapeutic Targets in a Pan-Cancer Study" Cancers 12, no. 7: 1816. https://doi.org/10.3390/cancers12071816