title: ATOH1 Can Regulate the Tumorigenicity of Gastric Cancer Cells by Inducing the Differentiation of Cancer Stem Cells.
abstract: Cancer stem cells (CSCs) have been shown to mediate tumorigenicity, chemo-resistance, radio-resistance and metastasis, which suggest they be considered therapeutic targets. Because their differentiated daughter cells are no longer tumorigenic, to induce the differentiation of CSCs can be one of strategies which can eradicate CSCs. Here we show that ATOH1 can induce the differentiation of gastric cancer stem cells (GCSCs). Real time PCR and western blot analysis showed that ATOH1 was induced during the differentiation of GCSCs. Furthermore, the lentivirus-induced overexpression of ATOH1 in GCSCs and in gastric cancer cell lines significantly induced differentiation, reduced proliferation and sphere formation, and reduced in vivo tumor formation in the subcutaneous injection and liver metastasis xenograft models. These results suggest ATOH1 be considered for the development of a differentiation therapy for gastric cancer.
authors.affiliation: Department of Anatomy, School of Medicine, Pusan National University, Pusan, Republic of Korea; Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Pusan, Republic of Korea.
authors.forename: Myoung-Eun
authors.initials: ME
authors.lastname: Han
authors.affiliation: Medical Genomics Research Center, KRIBB, Daejeon, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Baek
authors.affiliation: Department of Biochemistry, School of Medicine, Pusan National University, Pusan, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Medicine, Pusan National University, Pusan, Republic of Korea.
authors.forename: Chi-Dug
authors.initials: CD
authors.lastname: Kang
authors.affiliation: Department of Anatomy, School of Medicine, Pusan National University, Pusan, Republic of Korea.
authors.forename: Sae-Ock
authors.initials: SO
authors.lastname: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D025521:Tumor Suppressor Proteins; C500942:ATOH1 protein, human; C495500:RASSF4 protein, human