Epithelial mesenchymal interactions in cancer and development.

摘要: After the development of genetics as a science in What once was catalog functionally diverse proearly part twentieth century, anecdotal observa- teins associated puzzling ways with many different tions that some cancers run families raised suspicions pathologies is now beginning to gel into picture genes may lie at heart these diseases. Prog- few defined molecular events are common all ress began be made when, early 1980s, cancerous cells (Hanahan and Weinberg, 2000). These were shown altered versions normal cellu- events, self-sufficiency growth signals, insensitivity lar (Bishop, 1981, 1983; Varmus, 1984). However, inhibitory evasion programmed cell initial catalogs various can- death, limitless replicative potential, sustained angiocers did not provide clues how they caused genesis, tissue invasion metastasis, highlight disease. The issues stake time way six alterations physiology which think about them aptly summarized by J.M. most 2000) can Bishop: “what roles do cellular oncogenes play related breaks rules follow during daily affairs cells? Why there? We development. last two, angiogenesis know but it widely suspected figure features differentiation…(they) have revealed us aggressive lethal tumors require only touchstones carcinogenesis, lose contacts their neighbors, become control well.” Time has proven motile, invade surrounding territories where this speculation correct, finding proliferate undergo further invasive behavior. 1990s role for Ras assignment fates phase process morphoduring flies worms served logical transformation often referred epithelial timely encouraging an understanding mesenchymal transition (EMT). cancer might aided correlates played Epithelial Mesenchymal Transitions Their (Egan 1993). Developmental Constraints In parallel very stream inquiry, devel- EMTs transient changes structure opmental biologists had been pursuing years acquisition motile properway put organisms together. To this, ties. During development, closely regulated turned attention 20 large scale reorganization tissues years, crowned recent advent whole genome accompanies several morphogenetic e.g., sequencing, involved rich harvest directed movement coalescence mesodermal interesting proteins assemble networks gastrulation or migration neural crest information processing. studies from neuroepithelium. cancer, reprethat result net- sent first indication does recognize works up proteins. its neighbors vehicle propagation makeups human fly are, essence, same. through organism. Differences arise because conserved protein cells, must reflect failure species-specific programs gene expression mechanisms mediate cell-cell recognition A survey literature reveals coupling maintenance shape polarity. core developmental processing Therefore, basis undevice five signaling pathways: Delta/Notch, Wnt/ derlies definition durFrizzled, Hedgehog/Patched, TGFb/BMPs, RTKs, ing insight reguwhich interact multiple levels regulate latory activated process. processes. Ephrins receptors surface molecules