August 2008 Molecular Cancer Research Highlights

Selected Articles from the August 1, 2008 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the August 2008 issue of Molecular Cancer Research

Cadherin-11 in Prostate Cancer Metastasis

Chu et al.

Page 1259

Bone is the most common site of metastases from prostate cancer. However, the mechanism is not fully understood. Chu and colleagues show that the cell adhesion molecule cadherin-11 was highly expressed in prostate cancer cells derived from bone metastases. In clinical specimens, cadherin-11 was also expressed increasingly from primary to metastatic disease especially in bone. Chu and colleagues also show in a mouse model that the incidence of PC-3 metastasis to bone was reduced greatly when the cadherin-11 was knocked down by gene-specific shRNA, thus suggesting that cadherin-11 is involved in the metastasis of prostate cancer to bone.

GRP78 Protects Tumor Endothelial Cells

Virrey et al.

Page 1268

The stress chaperone GRP78/BiP has been studied extensively in tumors, but little is known about the role of this protein in the tumor vasculature.
Virrey and colleagues novel findings show that the glioma vasculature highly expresses GRP78, whereas blood vessels in the normal brain do not. These elevated GRP78 levels protect the tumor-associated endothelial cells from the cytotoxicity induced by standard-of-care chemotherapeutic drugs. Reducing GRP78 in tumor-associated endothelial cells increases their sensitivity to these therapeutic agents. The dual protective role of GRP78 in the tumor and tumor vasculature must be considered for optimal efficacy of anti-cancer therapy.

Sialyltransferase Involvements in Radiation Resistance

Lee et al.

Page 1316

Radiation induced the expression of sialyltransferases including β-galactoside α(2,6)-sialyltransferase (ST6Gal I). Protein sialylation by ST6Gal I, which has been frequently shown to be higher in cancer cells, is involved in the protein stability of integrin β1 and provides cellular radioresistance. Therefore, Lee and colleagues suggested that protein sialylation might be a novel target to overcome radio-resistance in radiation therapy. Radiation exposure was found to increase the sialylation of glycoproteins such as integrin β1 by inducing the expression of ST6Gal I, and increased protein sialylation contributed to cellular radiation resistance.

Bortezomib-Resistant NF-κB Activity in Myeloma Cells

Markovina et al.

Page 1356

The transcription factor NF-κB is important for multiple myeloma (MM) pathogenesis and drug resistance development, but the mechanisms regulating its activity in MM patients are not clearly understood. Although the best-characterized NF-κB activation mechanisms involve proteasomes, Markovina and colleagues found that a significant fraction of primary MM samples analyzed harbored proteasome inhibitor–resistant (termed PIR) NF-κB activity. This activity is further increased by patient-derived bone marrow stromal cells and correlates with resistance to bortezomib-induced apoptosis, suggesting that PIR NF-κB activity is prevalent and may present a novel pathway for targeted therapy of MM.

August 2008 Molecular Cancer Research Highlights

Selected Articles from the August 1, 2008 Issue

Cadherin-11 in Prostate Cancer Metastasis

GRP78 Protects Tumor Endothelial Cells

Sialyltransferase Involvements in Radiation Resistance

Bortezomib-Resistant NF-κB Activity in Myeloma Cells

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