title: HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer.
abstract: The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant progression in various types of cancer, but the mechanism underlying gastric carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a subset of human gastric cancer cells. HDAC6 knockdown caused the significant inhibition of gastric cancer cell growth without affecting the transition of cell cycles or the processing of cell death. We demonstrate that an increase in epidermal growth factor receptor (EGFR) signaling through decreased EGFR degradation was mediated by HDAC6 in gastric carcinogenesis. These results establish a molecular mechanism responsible for oncogenic HDAC6, explaining how EGFR signaling induced by the growth factor is sustained during the malignant progression of gastric cancer.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Bae
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Eun
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Hyung Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Woo Chan
authors.initials: WC
authors.lastname: Shin
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Hee Doo
authors.initials: HD
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Cancer Evolution Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Jueng Soo
authors.initials: JS
authors.lastname: You
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Cancer Evolution Research Center, The Catholic University of Korea, Seoul 137-701, Republic of Korea. Electronic address: swnam@catholic.ac.kr.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis; D002453:Cell Cycle; D016923:Cell Death; D045744:Cell Line, Tumor; D004705:Endocytosis; D011992:Endosomes; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C097227:RABEP1 protein, human; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: EGF receptor; Endocytosis; Histone deacetylase 6; Rabaptin-5