Autophagy

Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG Liang, C. et al. Nature Cell Biology 8, 688–698 (2006)

Autophagy, is involved in cellular responses to stress and starvation and in tumorigenesis. The tumour suppressor Beclin1 (BECN1) induces autophagy as part of the phosphatidylinositol 3 kinase class III (PI3KC3) complex. Liang et al. identify the candidate tumour suppressor UVRAG as part of the BECN1–PI3KC3 complex. UVRAG promotes autophagy and suppresses the tumorigenicity of HCT116 human colon cancer cells in mice. Furthermore, like BECN1, UVRAG is mono-allelically mutated in various human cancers.

Breast Cancer

Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGFR2) Gonzalez, R. et al. J. Biol. Chem 6 July 2006 (doi: 10.1074/jbc.M601991200)

Increased serum leptin levels correlate with obesity and increased risk of breast cancer, and levels of leptin and its receptor are increased in breast tumour tissue. Gonzalez et al. show that leptin increases the expression of VEGF, VEGFR2 and cyclin D1, which leads to increased proliferation in 4T1 mouse mammary tumour cells. Pretreatment of syngeneic mice with a small-peptide leptin receptor antagonist (LPrA2) slowed the growth of injected 4T1 cells and decreased tumour burden, indicating that leptin inhibitors might be useful breast cancer therapeutics.

Tumour Immunology

High numbers of tumor infiltrating FOXP3-positive regulatory T-cells are associated with improved overall survival in follicular lymphoma Carreras, J. et al. Blood 6 July 2006 (doi: 10.1182/blood-2006-04-018218)

Most patients with follicular lymphoma (FL, a subtype of adult B-cell non-Hodgkin lymphoma), have incurable disease that frequently develops resistance to therapy or transforms to aggressive diffuse large B-cell lymphoma (DLBCL). Carreras et al. examined samples from 97 patients at diagnosis and 37 at first relapse using an antibody to the regulatory-T-cell (Treg) marker FOXP3. Increased Treg numbers predicted improved survival, and Treg numbers were reduced on transformation of FL to DLBCL, which indicates that Tregs might modulate the host immune response and biological behaviour of FL.

Tumour Classification

A molecular correlate to the Gleason grading system for prostate adenocarcinoma. True, L., et al. Proc. Natl Acad. Sci. USA 103, 10881–10996 (2006)

The Gleason scoring system is based on the histological grade of tumours, dividing them into those that show well-differentiated or poorly differentiated features. Leroy Hood, Peter Nelson and colleagues have identified an 86-gene signature that distinguishes low-grade from high-grade prostate adenocarcinomas. Characterizing the molecular phenotype of histological grade is of potential clinical importance.