May 2008 Molecular Cancer Research Highlights

Selected Articles from the May 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 May 2008 issue of Molecular Cancer Research

Fn14 Promotes Malignant Behavior in Breast Cancer

Willis et al.

Page 725

The molecular basis of invasion and metastasis in breast cancer remains poorly understood. Willis and colleagues report a pivotal role for the Fn14 receptor as a promoter of invasive behavior. Expression of Fn14 in breast tumors correlated with several poor prognostic indicators, and Fn14 was most highly expressed in the ERBB2+/ER- intrinsic subtype. Manipulation of Fn14 expression levels in breast cancer cells altered invasive capacity, and Fn14-triggered invasion required NF-κB pathway activation. The Fn14 signaling axis shows promise as a novel clinical marker and therapeutic target for a subset of invasive breast tumors.

Gene Signature for Aggression of Melanoma Metastases

Xu et al.

Page 760

Metastasis is the deadliest phase of cancer progression. Xu and colleagues report the identification of a “metastasis aggressiveness gene expression signature” derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. It is shown that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. The importance of tumor-microenvironment interactions during metastasis is suggested. The findings of this report should contribute to the understanding, diagnosis, and treatment of malignant melanoma, which currently remains essentially untreatable.

Evasion of Decorin-Induced Growth Inhibition

Zafiropoulos et al.

Page 785

Decorin is an established natural oncosuppressive factor, which acts by inducing protracted EGFR internalization and attenuation of the respective intracellular signaling. Zafiropoulos and colleagues study showed that osteosarcoma cells are resistant to decorin-mediated cytostatic effects by a mechanism involving the protracted overexpression and phosphorylation of EGFR. The decorin-mediated attenuation of EGFR internalization did not require active EGFR signaling, showing that it is achieved through extracellular decorin-EGFR interaction and stabilization. In view of the proposed design of decorin-based anticancer therapeutic strategies, the study provides new data on pathways that cancer cells might employ to overcome the established decorin-induced growth suppression.

GSTP1 Gene Regulation by p53

Lo et al.

Page 843

The glutathione S-transferase P1, GSTP1, a major phase II-metabolizing enzyme and stress signaling regulator is overexpressed in many human tumors and the overexpression is associated with aggressive tumor growth and poor response to therapy. Lo and colleagues report here that the human GSTP1 gene contains functional p53-binding motifs and is a transcriptional target of the tumor suppressor, p53. Wild-type, but not mutant p53, transcriptionally activates gene expression via binding to the GSTP1 p53 binding sites. Malignant brain tumors with wild-type p53 consistently expressed higher levels of GSTP1 and were, in general, more resistant to the DNA crosslinking agent, cisplatin, than those with the mutant p53. The p53-mediated GSTP1 gene activation constitutes a novel, heretofore unrecognized, mechanism of protecting the genome and, potentially, of tumor drug resistance.

May 2008 Molecular Cancer Research Highlights

Selected Articles from the May 1, 2008 Issue

Fn14 Promotes Malignant Behavior in Breast Cancer

Gene Signature for Aggression of Melanoma Metastases

Evasion of Decorin-Induced Growth Inhibition

GSTP1 Gene Regulation by p53

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