Notch1 directly induced CD133 expression in human diffuse type gastric cancers
| Autor: | Yutaka Kondo, Hidetomo Konishi, Xiaoyi Jin, Nobuyuki Ara, Osamu Kimura, Takeshi Kanno, Naoki Asano, Tooru Shimosegawa, Kiyotaka Asanuma, Waku Hatta, Akira Imatani, Tomoyuki Koike |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty cancer stem cell Notch Cellular differentiation RBP-J kappa Biology medicine.disease_cause Transfection 03 medical and health sciences 0302 clinical medicine Cancer stem cell Stomach Neoplasms Cell Line Tumor medicine Cell Adhesion Humans AC133 Antigen CD133 Receptor Notch1 Promoter Regions Genetic Cell Proliferation Binding Sites Cell growth gastric cancer Cancer Cell Differentiation medicine.disease carbohydrates (lipids) Gene Expression Regulation Neoplastic 030104 developmental biology Phenotype Oncology 030220 oncology & carcinogenesis Immunoglobulin J Recombination Signal Sequence-Binding Protein embryonic structures Cancer research cardiovascular system Disease Progression Neoplastic Stem Cells sense organs Signal transduction biological phenomena cell phenomena and immunity Carcinogenesis Chromatin immunoprecipitation Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Hidetomo Konishi 1 , Naoki Asano 1 , Akira Imatani 1 , Osamu Kimura 1 , Yutaka Kondo 1 , Xiaoyi Jin 1 , Takeshi Kanno 1 , Waku Hatta 1 , Nobuyuki Ara 1 , Kiyotaka Asanuma 1 , Tomoyuki Koike 1 , Tooru Shimosegawa 1 1 Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi 980-8574, Japan Correspondence to: Akira Imatani, email: aimatani@med.tohoku.ac.jp Keywords: Notch, RBP-J kappa, cancer stem cell, gastric cancer, CD133 Received: June 04, 2016 Accepted: July 19, 2016 Published: July 30, 2016 ABSTRACT CD133 is considered as a stem-like cell marker in some cancers including gastric cancers, and Notch1 signaling is known to play an important role in the maintenance and differentiation of stem-like cells. We aimed to investigate whether Notch1 signaling contributes to the carcinogenesis of gastric cancers and CD133 induction. CD133 expression was detected in 51.4% of diffuse type gastric cancers while it was not detected in intestinal type gastric cancers. Similarly, only poorly-differentiated gastric cancer cell lines expressed CD133 and activated-Notch1. Inhibiting Notch1 signaling resulted in decreased CD133 expression, side population cells, cell proliferation and anchorage independent cell growth. Chromatin immunoprecipitation suggested that this Notch1 dependent regulation of CD133 was caused by direct binding of activated-Notch1 to the RBP-Jκ binding site in the 5′ promoter region of CD133 gene. In addition, knocking down RBP-Jκ reduced CD133 induction in activated-Notch1 transfected cells. These findings suggested that Notch1 signaling plays an important role in the maintenance of the cancer stem-like phenotype in diffuse type gastric cancer through an RBP-Jκ dependent pathway and that inhibiting Notch1 signaling could be an effective therapy against CD133 positive diffuse type gastric cancers. |
| Databáze: | OpenAIRE |
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