KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer.

Abstract

Recent efforts to sequence human cancer genomes have highlighted that point mutations in genes involved in the epigenetic setting occur in tumor cells. Small cell lung cancer (SCLC) is an aggressive tumor with poor prognosis, where little is known about the genetic events related to its development. Herein, we have identified the presence of homozygous deletions of the candidate histone acetyltransferase KAT6B, and the loss of the corresponding transcript, in SCLC cell lines and primary tumors. Furthermore, we show, in vitro and in vivo, that the depletion of KAT6B expression enhances cancer growth, while its restoration induces tumor suppressor-like features. Most importantly, we demonstrate that KAT6B exerts its tumor-inhibitory role through a newly defined type of histone H3 Lys23 acetyltransferase activity.

• Authors: Laia Simó-Riudalbas, Montserrat Pérez-Salvia, Fernando Setien, Alberto Villanueva, Catia Moutinho, Anna Martínez-Cardús, Sebastian Moran, Maria Berdasco, Antonio Gomez, Enrique Vidal, Marta Soler, Holger Heyn, Alejandro Vaquero, Carolina de la Torre, Silvia Barceló-Batllori, August Vidal, Luca Roz, Ugo Pastorino, Katalin Szakszon, Guntram Borck, Conceição S Moura, Fátima Carneiro, Ilse Zondervan, Suvi Savola, Reika Iwakawa, Takashi Kohno, Jun Yokota, Manel Esteller
• Journal: Cancer research (Cancer Res) Vol. 75 Issue 18 Pg. 3936-45 (Sep 15 2015) ISSN: 1538-7445 [Electronic] United States
• PMID: 26208904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Alkylating
• Histones
• Neoplasm Proteins
• RNA, Messenger
• RNA, Neoplasm
• RNA, Small Interfering
• Irinotecan
• Histone Acetyltransferases
• KAT6B protein, human
• Camptothecin

Topics

• Acetylation
• Animals
• Antineoplastic Agents, Alkylating (pharmacology, therapeutic use)
• Camptothecin (analogs & derivatives, pharmacology, therapeutic use)
• Carcinoma, Small Cell (drug therapy, enzymology, genetics, pathology)
• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Drug Resistance, Neoplasm
• Gene Deletion
• Gene Expression Profiling
• Genes, Tumor Suppressor
• Heterografts
• Histone Acetyltransferases (deficiency, genetics, physiology)
• Histones (metabolism)
• Humans
• Irinotecan
• Lung Neoplasms (drug therapy, enzymology, genetics, pathology)
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Neoplasm Proteins (deficiency, genetics, physiology)
• Protein Processing, Post-Translational
• RNA Interference
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)
• RNA, Small Interfering (pharmacology)