Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis.

Abstract:

BACKGROUND:In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. RESULTS:In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. CONCLUSIONS:These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Lee SY,Jeon HM,Kim CH,Ju MK,Bae HS,Park HG,Lim SC,Han SI,Kang HS

doi

10.1186/1476-4598-10-113

subject

Has Abstract

pub_date

2011-09-14 00:00:00

pages

113

issn

1476-4598

pii

1476-4598-10-113

journal_volume

10

pub_type

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