Skip to Content
Merck
  • Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma.

Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma.

Oncotarget (2014-09-28)
Yona Goldshmit, Sari Schokoroy Trangle, Yoel Kloog, Ronit Pinkas-Kramarski
ABSTRACT

The three oncogenes, ErbB receptors, Ras proteins and nucleolin may contribute to malignant transformation. Previously, we demonstrated that nucleolin could bind both Ras protein and ErbB receptors. We also showed that the crosstalk between the three proteins facilitates anchorage independent growth and tumor growth in nude mice, and that inhibition of this interaction in prostate and colon cancer cells reduces tumorigenicity. In the present study, we show that treatment with Ras and nucleolin inhibitors reduces the oncogenic effect induced by ErbB1 receptor in U87-MG cells. This combined treatment enhances cell death, reduces cell proliferation and cell migration. Moreover, we demonstrate a pivotal role of nucleolin in ErbB1 activation by its ligand. Nucleolin inhibitor prevents EGF-induced receptor activation and its downstream signaling followed by reduced proliferation. Furthermore, inhibition of Ras by Salirasib (FTS), mainly reduces cell viability and motility. The combined treatment, which targets both Ras and nucleolin, additively reduces tumorigenicity both in vitro and in vivo. These results suggest that targeting both nucleolin and Ras may represent an additional opportunity for inhibiting cancers, including glioblastoma, that are driven by these oncogenes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Boric acid-11B, ≥99 atom % 11B
Sigma-Aldrich
Boric acid, 99.999% trace metals basis
Sigma-Aldrich
Boric acid, 99.97% trace metals basis
Sigma-Aldrich
Methylene Blue solution, for microscopy, concentrate according to Ehrlich, concentrated, aqueous solution
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Boric acid, BioReagent, for molecular biology, suitable for cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
Boric acid, suitable for electrophoresis, ≥99.5%
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Methylene blue, certified by the Biological Stain Commission
Sigma-Aldrich
Methylene Blue solution, for microscopy
Sigma-Aldrich
L-Glutamine
Supelco
L-Glutamine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Methylene Blue solution, suitable for microbiology
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
Boric acid, tablet, 1 g boric acid per tablet
Sigma-Aldrich
Boric acid, BioXtra, ≥99.5%
Sigma-Aldrich
Boric acid, BioUltra, for molecular biology, ≥99.5% (T)
SAFC
L-Glutamine
Sigma-Aldrich
Boric acid, puriss., meets analytical specification of Ph. Eur., BP, NF, 99.5-100.5%, powder
Sigma-Aldrich
Boric acid, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Boric acid, ACS reagent, ≥99.5%
Supelco
Benalaxyl-M, PESTANAL®, analytical standard
Sigma-Aldrich
L-Glutamine, Vetec, reagent grade, ≥99%
Sigma-Aldrich
Boric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., buffer substance, ≥99.8%