%0 Journal Article
%T Induction of HSPA4 and HSPA14 by NBS1 overexpression contributes to NBS1-induced in vitro metastatic and transformation activity
%A Chung-Yin Wu
%A Chih-Ta Lin
%A Min-Zu Wu
%A Kou-Juey Wu
%J Journal of Biomedical Science
%D 2011
%I BioMed Central
%R 10.1186/1423-0127-18-1
%X RT-PCR, Western blot analysis, in vitro migration/invasion, soft agar colony formation, and gelatin zymography assays were performed.Here we show that heat shock protein family members, A4 and A14, were induced by NBS1 overexpression. siRNA mediated knockdown of HSPA4 or HSPA14 decreased the in vitro migration, invasion, and transformation activity in H1299 cells overexpressing NBS1. However, HSPA4 or HSPA14 induced activity was not mediated through MMP2. NBS1 overexpression induced the expression of heat shock transcription factor 4b (HSF4b), which correlated with the expression of HSPA4 and HSPA14.These results identify a novel pathway (NBS1-HSF4b-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBS1 overexpression.Nijmegen breakage syndrome (NBS) is a chromosomal-instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation [1-3]. The NBS gene product, NBS1 (p95 or nibrin), is a part of the MRN complex, a central player associated with DNA double-strand break (DSB) repair [1,2]. NBS1 carries out its checkpoint functions when it is phosphorylated by ATM (ataxia-telangiectasia mutated) protein after ionizing radiation [4-6]. We previously demonstrated that c-MYC, a dominant oncoprotein, directly activates NBS1 expression [7]. The proliferation-inducing function of NBS1 is supported by the phenotypes of diminished expansion of the inner cell mass of mutant blastocysts (Nbs1 null) and cellular proliferation defects in Nbs1m/m mouse embryonic fibroblasts (MEFs) [8-10]. NBS1 overexpression induces/enhances transformation activity through the activation of PI 3-kinase/Akt [11], indicating that overexpression of NBS1 is an oncogenic event. Increased NBS1 expression is also a prognostic factor for advanced stage head and neck squamous cell carcinoma (HNSCC) [12]. NBS1 interacts with the p110 subunits of PI 3-kinase to activate PI 3-ki
%U http://www.jbiomedsci.com/content/18/1/1