LOXL1 and LOXL4 are epigenetically silenced and can inhibit Ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer

Guojun Wu, Zhongmin Guo, Xiaofei Chang, Sook Kim Myoung, Jatin K. Nagpal, Junwei Liu, Joni M. Maki, Kari I. Kivirikko, Stephen P. Ethier, Barry Trink, David Sidransky

Research output: Contribution to journalArticlepeer-review

Abstract

Promoter hypermethylation is one of the common mechanisms leading to gene silencing in various human cancers. Using a combination of pharmacologic unmasking and microarray techniques, we identified 59 candidate hypermethylated genes, including LOXL1, a lysyl oxidase-like gene, in human bladder cancer cells. We further showed that LOXL1 and LOXL4 are commonly silenced genes in human bladder cancer cells, and this silence is predominantly related to promoter methylation. We also found LOXL1 and LOXL4 gene methylation and loss of expression in primary bladder tumors. In addition, somatic mutations were identified in LOXL4, but not in LOXL1 in bladder cancer. Moreover, reintroduction of LOXL1 and LOXL4 genes into human bladder cancer cells leads to a decrease of colony formation ability. Further studies indicated that the overexpression of LOXL1 and LOXL4 could antagonize Ras in activating the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, our current study suggests for the first time that lysyl oxidase-like genes can act as tumor suppressor genes and exert their functions through the inhibition of the Ras/ERK signaling pathway in human bladder cancer.

Original languageEnglish (US)
Pages (from-to)4123-4129
Number of pages7
JournalCancer Research
Volume67
Issue number9
DOIs
StatePublished - May 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'LOXL1 and LOXL4 are epigenetically silenced and can inhibit Ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer'. Together they form a unique fingerprint.

Cite this