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Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling.
Hayakawa, Yoku; Sakitani, Kosuke; Konishi, Mitsuru; Asfaha, Samuel; Niikura, Ryota; Tomita, Hiroyuki; Renz, Bernhard W; Tailor, Yagnesh; Macchini, Marina; Middelhoff, Moritz; Jiang, Zhengyu; Tanaka, Takayuki; Dubeykovskaya, Zinaida A; Kim, Woosook; Chen, Xiaowei; Urbanska, Aleksandra M; Nagar, Karan; Westphalen, Christoph B; Quante, Michael; Lin, Chyuan-Sheng; Gershon, Michael D; Hara, Akira; Zhao, Chun-Mei; Chen, Duan; Worthley, Daniel L; Koike, Kazuhiko; Wang, Timothy C.
Afiliación
  • Hayakawa Y; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Sakitani K; Department of Gastroenterology, Graduate school of Medicine, the University of Tokyo, Tokyo, 1138655, Japan.
  • Konishi M; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Asfaha S; Department of Gastroenterology, Graduate school of Medicine, the University of Tokyo, Tokyo, 1138655, Japan.
  • Niikura R; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Tomita H; Department of Medicine, University of Western Ontario, London, ON N6A 5W9, Canada.
  • Renz BW; Department of Gastroenterology, Graduate school of Medicine, the University of Tokyo, Tokyo, 1138655, Japan.
  • Tailor Y; Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, 5011194, Japan.
  • Macchini M; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Middelhoff M; Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Munich, 81377, Germany.
  • Jiang Z; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Tanaka T; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Dubeykovskaya ZA; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Kim W; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Chen X; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Urbanska AM; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Nagar K; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Westphalen CB; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Quante M; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Lin CS; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Gershon MD; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Hara A; Department of Internal Medicine III, Klinikum der Universität München, Munich, 81377, Germany.
  • Zhao CM; Department of Internal Medicine II, Klinikum rechts der Isar, II. Technische Universität München, Munich, 81675, Germany.
  • Chen D; Department of Pathology and Cell Biology, Columbia University, New York, NY, 10032, USA.
  • Worthley DL; Transgenic Mouse Shared Resource, Columbia University, New York, NY, 10032, USA.
  • Koike K; Department of Pathology and Cell Biology, Columbia University, New York, NY, 10032, USA.
  • Wang TC; Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, 5011194, Japan.
Cancer Cell ; 31(1): 21-34, 2017 01 09.
Article en En | MEDLINE | ID: mdl-27989802
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 an ACh muscarinic receptor-3 (M3R)-dependent manner, in part through suppression of yes-associated protein (YAP) function. This feedforward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias Gástricas / Transducción de Señal / Acetilcolina / Factor de Crecimiento Nervioso Límite: Animals Idioma: En Revista: Cancer cell Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias Gástricas / Transducción de Señal / Acetilcolina / Factor de Crecimiento Nervioso Límite: Animals Idioma: En Revista: Cancer cell Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos