Main description:

Oncogenes and tumor suppressor genes had been traditionally studied in the context of cell proliferation, differentiation, senescence, and survival, four relatively cell-autonomous processes. Consequently, in the late '80s-early '90s, neoplastic growth was described largely as an imbalance between net cell accumulation and loss, brought about through mutations in cancer genes. In the last ten years, a more holistic understanding of cancer has slowly emerged, stressing the importance of interactions between neoplastic and various stromal components: extracellular matrix, basement membranes, fibroblasts, endothelial cells of blood and lymphatic vessels, tumor-infiltrating lymphocytes, etc. The commonly held view is that changes in tumor microenvironment are "soft-wired", i.e., epigenetic in nature and often reversible. Yet, there exists a large body of evidence suggesting that well-known mutations in cancer genes profoundly affect tumor milieu. In fact, these non-cell-autonomous changes might be one of the primary reasons such mutations are preserved in late-stage tumors.

Contents:

Part One: Opening remarks

Hardwiring tumor progression (Andrei Thomas-Tikhonenko)

Part Two: Breaking away: Epithelial-mesenchymal transition

PI3K/AKT pathway and the epithelial-mesenchymal transition (Alfonso Bellacosa and Lionel Larue)

Loss of cadherin-catenin adhesion system in invasive cancer cells (Wen-Hui Lien and Valeri Vasioukhin)

Rho GTPases in regulation of cancer cell motility, invasion, and microenvironment (Donita Brady, Jamie Alan, and Adrienne Cox)

Merlin/NF2 tumor suppressor and Ezrin-Radixin-Moesin (ERM) proteins in cancer development and progression (Ling Ren and Chand Khanna)

Part Three: Coming up for air: Hypoxia and Angiogenesis

von Hippel-Lindau tumor suppressor, hypoxia-induced factor-1, and tumor vascularization (Huafeng Zhang and Gregg Semenza)

RAS oncogenes and tumor-vascular interface (Janusz Rak)

Myc and control of tumor neovascularization (Prema Sundaram, Chi V. Dang, and Andrei Thomas-Tikhonenko)

p53 and angiogenesis (Jose Teodoro, Sara Evans, and Michael Green)

Ink4a locus: beyond cell cycle (Gregory Enders)

Part Four: Gaining new ground: Metastasis and stromal cell interactions

NM23 as a metastasis inhibitor (Rajeev Kaul, Masanao Murakami, Pankaj Kumar, and Erle Robertson)

HGF/c-MET signaling in advanced cancers (Mandira Ray, JG Garcia, and Ravi Salgia)

Contribution of ADAMs and ADAMTSs to tumor expansion and metastasis (Antoni Xavier Torres-Collado and Luisa Iruela-Arispe)

Stromal cells & tumor milieu: PDGF et al (Michele Jacob and Ellen Pure)

Tgf-beta signaling alterations in neoplastic and stromal cells (Qinghua Zeng and Boris Pasche)

Part Five: Getting attention: Immunerecognition and inflammation

Genetic Instability and Chronic Inflammation in Gastrointestinal Cancers (Antonia Sepulveda and John Lynch)

Immunoglobulin gene rearrangements, oncogenic translocations, B-cell receptor signaling, and B-lymphomagenesis (Murali Gururajan and Subbarao Bondada)

Modulation of Philadelphia chromosome-positive hematological malignancies by bone marrow microenvironment (Lin Wang, Heather O'Leary, and Laura Gibson)

Part 6: Putting it all together

Melanoma: mutations in multiple pathways at the tumor-stroma interface (Himabindu Gaddipati and Meenhard Herlyn)

Cooperation and Cancer (Kathleen Sprouffske and Carlo Maley, Wistar Institute)