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.

Reviews how tumor microenvironment and progression are hard-wired at the genetic level Includes supplementary material: sn.pub/extras

Inhalt
Opening Remarks.- Hardwiring Tumor Progression.- Breaking Away: Epithelial-Mesenchymal Transition.- PI3K/AKT Pathway and the Epithelial-Mesenchymal Transition.- Loss of Cadherin-Catenin Adhesion System in Invasive Cancer Cells.- Rho GTPases in Regulation of Cancer Cell Motility, Invasion, and Microenvironment.- Merlin/NF2 Tumor Suppressor and EzrinRadixinMoesin (ERM) Proteins in Cancer Development and Progression.- Coming up for Air: Hypoxia and Angiogenesis.- von Hippel-Lindau Tumor Suppressor, Hypoxia-Inducible Factor-1, and Tumor Vascularization.- RAS Oncogenes and Tumor-Vascular Interface.- Myc and Control of Tumor Neovascularization.- p53 and Angiogenesis.- Ink4a Locus: Beyond Cell Cycle.- Gaining New Ground: Metastasis and Stromal Cell Interactions.- Nm23 as a Metastasis Inhibitor.- HGF/c-MET Signaling in Advanced Cancers.- Contribution of ADAMs and ADAMTSs to Tumor Expansion and Metastasis.- Stromal Cells and Tumor Milieu: PDGF et al..- TGF-? Signaling Alterations in Neoplastic and Stromal Cells.- Getting Attention: Immune Recognition and Inflammation.- Genetic Instability and Chronic Inflammation in Gastrointestinal Cancers.- Immunoglobulin Gene Rearrangements, Oncogenic Translocations, B-Cell Receptor Signaling, and B Lymphomagenesis.- Modulation of Philadelphia Chromosome-Positive Hematological Malignancies by the Bone Marrow Microenvironment.- Putting It All Together.- Melanoma: Mutations in Multiple Pathways at the Tumor-Stroma Interface.- Cooperation and Cancer.