Dissection of signal-regulated transcriptional modules by signaling pathway interference inoncogene-transformed cells

摘要

Complex signal transduction processes arc involved in almost any aspect of cancer cell biology. Signal transduction from the cell membrane to the nucleus comprises the regulated interaction of surface receptors, intracellular effector enzymes, transcripiional regulators and the protein synthesis machinery. Signal transduction is involved in normal physiologic and developmental processes. Signaling permits cells to respond to changes in their microenvironment. External stimuli are coupled to the induction of specific gene expression programs required for mitogencsis, proliferation, differentiation and development. Cancer cells, however, acquire their own growth-signaling pathways, independent of external signals. Malignant proliferation can be stimulated by overexpression of membrane receptors or by activating mutations in downstream effector proteins. Thus, oneogenic signal transduction in tumor cells mimicks the continuous availability of growth and survival factors. As a result, gene transcription is subject to untimely and long-lasting alterations.