The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling
Open accessAbstract
Summary Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1+ cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in a muscarinic acetylcholine receptor-3 (M3R)-dependent manner, in part through suppression of Yes-Associated Protein (YAP) function. This feed-forward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.
Overview
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
Cites
Statistics
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Méndez-Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G. N., & Frenette, P. S. (2010) · Nature · doi:10.1038/nature09262 · Cited by 3,374
Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.037 · Cited by 1,628
Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow
Katayama, Y., Battista, M., Kao, W.-M., Hidalgo, A., Peired, A. J., Thomas, S. A., & Frenette, P. S. (2006) · Cell · doi:10.1016/j.cell.2005.10.041 · Cited by 1,412
Autonomic nerve development contributes to prostate cancer progression
Magnon, C., Hall, S. J., Lin, J., Xue, X., Gerber, L., Freedland, S. J., & Frenette, P. S. (2013) · Science · doi:10.1126/science.1236361 · Cited by 1,287
Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit
von Moltke, J., Ji, M., Liang, H.-E., & Locksley, R. M. (2016) · Nature · doi:10.1038/nature16161 · Cited by 1,230
YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response
Azzolin, L., Panciera, T., Soligo, S., Enzo, E., Bicciato, S., Dupont, S., Bresolin, S., Frasson, C., Basso, G., Guzzardo, V., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.013 · Cited by 1,094
Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion
Venkatesh, H. S., Johung, T. B., Caretti, V., Noll, A., Tang, Y., Nagaraja, S., Gibson, E. M., Mount, C. W., Polepalli, J., Mitra, S. S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.012 · Cited by 963
β-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis
Rosenbluh, J., Nijhawan, D., Cox, A. G., Li, X., Neal, J. T., Schafer, E. J., Zack, T. I., Wang, X., Tsherniak, A., Schinzel, A. C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.026 · Cited by 757
Neural stem and progenitor cells in nestin‐GFP transgenic mice
Mignone, J. L., Kukekov, V., Chiang, A., Steindler, D., & Enikolopov, G. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.10964 · Cited by 704
Denervation suppresses gastric tumorigenesis
Zhao, C.-M., Hayakawa, Y., Kodama, Y., Muthupalani, S., Westphalen, C. B., Andersen, G. T., Flatberg, A., Johannessen, H., Friedman, R. A., Renz, B. W., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009569 · Cited by 668
Self-citationYap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer
Gregorieff, A., Liu, Y., Inanlou, M. R., Khomchuk, Y., & Wrana, J. L. (2015) · Nature · doi:10.1038/nature15382 · Cited by 648
TRKing Down an Old Oncogene in a New Era of Targeted Therapy
Vaishnavi, A., Le, A. T., & Doebele, R. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0765 · Cited by 642
A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer
Jiao, S., Wang, H., Shi, Z., Dong, A., Zhang, W., Song, X., He, F., Wang, Y., Zhang, Z., Wang, W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.010 · Cited by 602
Feng, X., Degese, M. S., Iglesias-Bartolome, R., Vaque, J. P., Molinolo, A. A., Rodrigues, M., Zaidi, M. R., Ksander, B. R., Merlino, G., Sodhi, A., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.016 · Cited by 563
Quante, M., Bhagat, G., Abrams, J. A., Marache, F., Good, P., Lee, M., Lee, Y., Friedman, R. A., Asfaha, S., Dubeykovskaya, Z. A., et al. (2012) · Cancer Cell · doi:10.1016/j.ccell.2026.07.005 · Cited by 486
Self-citationMutant Gq/11 Promote Uveal Melanoma Tumorigenesis by Activating YAP
Yu, F.-X., Luo, J., Mo, J.-S., Liu, G., Kim, Y. C., Meng, Z., Zhao, L., Peyman, G., Ouyang, H., Jiang, W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.017 · Cited by 463
Self-citationBrownell, I., Guevara, E., Bai, C. B., Loomis, C. A., & Joyner, A. L. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.02.021 · Cited by 453
Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture
Li, X., Nadauld, L., Ootani, A., Corney, D. C., Pai, R. K., Gevaert, O., Cantrell, M. A., Rack, P. G., Neal, J. T., Chan, C. W.-M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3585 · Cited by 442
Long-lived intestinal tuft cells serve as colon cancer–initiating cells
Westphalen, C. B., Asfaha, S., Hayakawa, Y., Takemoto, Y., Lukin, D. J., Nuber, A. H., Brandtner, A., Setlik, W., Remotti, H., Muley, A., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73434 · Cited by 389
Self-citationHanoun, M., Zhang, D., Mizoguchi, T., Pinho, S., Pierce, H., Kunisaki, Y., Lacombe, J., Armstrong, S. A., Dührsen, U., & Frenette, P. S. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.06.020 · Cited by 381
Peterson, S. C., Eberl, M., Vagnozzi, A. N., Belkadi, A., Veniaminova, N. A., Verhaegen, M. E., Bichakjian, C. K., Ward, N. L., Dlugosz, A. A., & Wong, S. Y. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.02.006 · Cited by 368
Microbiota controls the homeostasis of glial cells in the gut lamina propria
Kabouridis, P. S., Lasrado, R., McCallum, S., Chng, S. H., Snippert, H. J., Clevers, H., Pettersson, S., & Pachnis, V. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.037 · Cited by 358
Hayakawa, Y., Ariyama, H., Stancikova, J., Sakitani, K., Asfaha, S., Renz, B. W., Dubeykovskaya, Z. A., Shibata, W., Wang, H., Westphalen, C. B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.003 · Cited by 328
Self-citationBailey, J. M., Alsina, J., Rasheed, Z. A., McAllister, F. M., Fu, Y., Plentz, R., Zhang, H., Pasricha, P. J., Bardeesy, N., Matsui, W., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2013.09.050 · Cited by 312
Gautam, D., Han, S.-J., Hamdan, F. F., Jeon, J., Li, B., Li, J. H., Cui, Y., Mears, D., Lu, H., Deng, C., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.009 · Cited by 299 · cited 2×
“Mist1-CreERT2 (Shi et al., 2009), Dclk1-CreERT (Westphalen et al., 2014), Tff2-Cre (Dubeykovskaya et al., 2016), Chrm3flox (Gautam et al., 2006), Chrm3 knockout (Aihara et al., 2003), Adrb2flox (Hinoi et al., 2008), and NesGFP (Mignone et al., 2004) mice were described previously.”
Hinoi, E., Gao, N., Jung, D. Y., Yadav, V., Yoshizawa, T., Myers, M. G., Chua, S. C., Kim, J. K., Kaestner, K. H., & Karsenty, G. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809113 · Cited by 267
Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration
Mahmoud, A. I., O’Meara, C. C., Gemberling, M., Zhao, L., Bryant, D. M., Zheng, R., Gannon, J. B., Cai, L., Choi, W.-Y., Egnaczyk, G. F., et al. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.06.017 · Cited by 261
Bezençon, C., Fürholz, A., Raymond, F., Mansourian, R., Métairon, S., Le Coutre, J., & Damak, S. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21768 · Cited by 251
Neuroplastic Changes Occur Early in the Development of Pancreatic Ductal Adenocarcinoma
Stopczynski, R. E., Normolle, D. P., Hartman, D. J., Ying, H., DeBerry, J. J., Bielefeldt, K., Rhim, A. D., DePinho, R. A., Albers, K. M., & Davis, B. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2050 · Cited by 212
da Penha Berzaghi, M., Cooper, J., Castren, E., Zafra, F., Sofroniew, M., Thoenen, H., & Lindholm, D. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03818.1993 · Cited by 207
Tallini, Y. N., Shui, B., Greene, K. S., Deng, K.-Y., Doran, R., Fisher, P. J., Zipfel, W., & Kotlikoff, M. I. (2006) · Physiological Genomics · doi:10.1152/physiolgenomics.00092.2006 · Cited by 197
Dual role of YAP and TAZ in renewal of the intestinal epithelium
Imajo, M., Ebisuya, M., & Nishida, E. (2015) · Nature Cell Biology · doi:10.1038/ncb3084 · Cited by 193
Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes
Albo, D., Akay, C. L., Marshall, C. L., Wilks, J. A., Verstovsek, G., Liu, H., Agarwal, N., Berger, D. H., & Ayala, G. E. (2011) · Cancer · doi:10.1002/cncr.26117 · Cited by 184
Cai, J., Maitra, A., Anders, R. A., Taketo, M. M., & Pan, D. (2015) · Genes & Development · doi:10.1101/gad.264515.115 · Cited by 175
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer
Dubeykovskaya, Z., Si, Y., Chen, X., Worthley, D. L., Renz, B. W., Urbanska, A. M., Hayakawa, Y., Xu, T., Westphalen, C. B., Dubeykovskiy, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms10517 · Cited by 169
Self-citationShi, G., Zhu, L., Sun, Y., Bettencourt, R., Damsz, B., Hruban, R. H., & Konieczny, S. F. (2009) · Gastroenterology · doi:10.1053/j.gastro.2008.12.066 · Cited by 168
Neuronal Serotonin Regulates Growth of the Intestinal Mucosa in Mice
Gross, E. R., Gershon, M. D., Margolis, K. G., Gertsberg, Z. V., & Cowles, R. A. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.05.007 · Cited by 166
Self-citationSong, P., Sekhon, H. S., Lu, A., Arredondo, J., Sauer, D., Gravett, C. A., Mark, G. P., Grando, S. A., & Spindel, E. R. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2484 · Cited by 149
tz, B. S. ⁄., Jurastow, I., Bader, S., Ringer, C., von Engelhardt, J., Chubanov, V., Gudermann, T. W., Diener, M., Kummer, W., Krasteva‐Christ, G., et al. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00087 · Cited by 122
Bannwarth, B., & Kostine, M. (2014) · Drugs · doi:10.1007/s40265-014-0208-6 · Cited by 122
Oesophageal adenocarcinoma and gastric cancer: should we mind the gap?
Hayakawa, Y., Sethi, N. S., Sepulveda, A. R., Bass, A. J., & Wang, T. C. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.24 · Cited by 122
Self-citationCeyhan, G. O., Schäfer, K., Kerscher, A. G., Rauch, U., Demir, İ. E., Kadıhasanoğlu, M., Böhm, C., Müller, M. W., Büchler, M. W., Giese, N. A., et al. (2010) · Annals of Surgery · doi:10.1097/sla.0b013e3181d974d4 · Cited by 120
CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis
Hayakawa, Y., Jin, G., Wang, H., Chen, X., Westphalen, C. B., Asfaha, S., Renz, B. W., Ariyama, H., Dubeykovskaya, Z. A., Takemoto, Y., et al. (2014) · Gut · doi:10.1136/gutjnl-2014-307190 · Cited by 113
Self-citationRaufman, J., Samimi, R., Shah, N., Khurana, S., Shant, J., Drachenberg, C., Xie, G., Wess, J., & Cheng, K. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6810 · Cited by 109
Okumura, T., Ericksen, R. E., Takaishi, S., Wang, S. S. W., Dubeykovskiy, Z., Shibata, W., Betz, K. S., Muthupalani, S., Rogers, A. B., Fox, J. G., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1506 · Cited by 93
Self-citationLapchak, P. A., Araujo, D. M., & Hefti, F. F. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90407-7 · Cited by 82
Lgr5+ Gastric Stem Cells Divide Symmetrically to Effect Epithelial Homeostasis in the Pylorus
Leushacke, M., Ng, A., Galle, J., Loeffler, M., & Barker, N. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.025 · Cited by 78
An effect of nerve growth factor on parasympathetic neurite outgrowth.
Collins, F., & Dawson, A. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.7.2091 · Cited by 77
Weeraratna, A. T., Dalrymple, S. L., Lamb, J. C., Denmeade, S. R., Miknyoczki, S. J., Dionne, C. A., & Isaacs, J. T. (2001) · PubMed · Cited by 77
Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion
Belo, A., Cheng, K., Chahdi, A., Shant, J., Xie, G., Khurana, S., & Raufman, J. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00306.2010 · Cited by 77
Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves
Lundgren, O., Jodal, M., Jansson, M., Ryberg, A. T., & Svensson, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016295 · Cited by 67
Nestin‐expressing cells in the gut give rise to enteric neurons and glial cells
Belkind‐Gerson, J., Carreón‐Rodríguez, A., Benedict, L. A., Steiger, C. E., Pieretti, A. C., Nagy, N., Dietrich, J., & Goldstein, A. M. (2012) · Neurogastroenterology & Motility · doi:10.1111/nmo.12015 · Cited by 61
Aihara, T., Fujishita, T., Kanatani, K., Furutani, K., Nakamura, E., Taketo, M. M., Matsui, M., Chen, D., & Okabe, S. (2003) · Gastroenterology · doi:10.1053/j.gastro.2003.09.018 · Cited by 52
Self-citationDclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal
Chandrakesan, P., May, R. J., Qu, D., Weygant, N., Taylor, V. E., Li, J. D., Ali, N., Sureban, S. M., Qante, M., Wang, T. C., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5129 · Cited by 50
Self-citationAihara, T., Nakamura, Y., Taketo, M. M., Matsui, M., & Okabe, S. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00514.2004 · Cited by 49
Mapping 5-HT inputs to enteric neurons of the guinea-pig small intestine
Neal, K., & Bornstein, J. C. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.12.017 · Cited by 45
An effect of nerve growth factor on the parasympathetic ciliary ganglion
Collins, F. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-05-01281.1984 · Cited by 34
Howard, L., Wyatt, S. L., Nagappan, G., & Davies, A. M. (2013) · Development · doi:10.1242/dev.085266 · Cited by 32
Kniewallner, K. M., Grimm, N., & Humpel, C. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.05.033 · Cited by 26
Phenotype and distribution pattern of nestin-GFP-expressing cells in murine myenteric plexus
Grundmann, D., Markwart, F., Scheller, A., Kirchhoff, F., & Schäfer, K. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2476-9 · Cited by 21
Cited by
Haematopoietic stem cell activity and interactions with the niche
Pinho, S., & Frenette, P. S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0103-9 · Cited by 984
β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer
Renz, B. W., Takahashi, R., Tanaka, T., Macchini, M., Hayakawa, Y., Dantes, Z., Maurer, H. C., Chen, X., Jiang, Z., Westphalen, C. B., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.11.007 · Cited by 543
Self-citationQuantitative evidence for early metastatic seeding in colorectal cancer
Hu, Z., Ding, J., Ma, Z., Sun, R., Seoane, J. A., Scott Shaffer, J., Suarez, C. J., Berghoff, A. S., Cremolini, C., Falcone, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0423-x · Cited by 490
A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling
Schneider, C., O’Leary, C. E., von Moltke, J., Liang, H.-E., Ang, Q. Y., Turnbaugh, P. J., Radhakrishnan, S., Pellizzon, M., Ma, A., & Locksley, R. M. (2018) · Cell · doi:10.1016/j.cell.2018.05.014 · Cited by 478
Zahalka, A. H., & Frenette, P. S. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0237-2 · Cited by 470
Metadata
- Authors
- Hayakawa, Y., Sakitani, K., Konishi, M., Asfaha, S., Niikura, R., Tomita, H., Renz, B. W., Tailor, Y., Macchini, M., Middelhoff, M., Jiang, Z., Tanaka, T., Dubeykovskaya, Z. A., Kim, W., Chen, X., Urbanska, A. M., Nagar, K., Westphalen, C. B., Quante, M., Lin, C.-S., Gershon, M. D., Hara, A., Zhao, C.-M., Chen, D., Worthley, D. L., Koike, K., & Wang, T. C.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 31
- Issue
- 1
- Pages
- 21-34
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2562236228
- Cited by
- 573
- References
- 61
- FWCI
- 22.77
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
