Cell signaling

Cells communicate and respond to the extracellular environment through a process designated signal transduction. Signal molecules bind to transmembrane receptors that span the cell membrane. The interaction of signal molecules with components of receptors located outside the cell modifies the intracellular components of the receptors. An environmental signal is thereby transduced into a cascade of regulatory steps that control genes which control cell proliferation and specialized properties of cells.

In some signaling pathways, scaffold proteins assemble signaling molecules into complexes for the initial passage of information from the transmembrane receptor to relay and adaptor proteins. Subsequent steps in the signaling process amplify and integrate signals. A chain of intracellular signaling proteins processes regulatory information through the cytoplasm and into the cell nucleus to activate or suppress genes. In other signaling pathways the regulatory cascades are abbreviated. The transduction of regulatory information from the intracellular component of the transmembrane receptor is more direct, circumventing intermediary steps in information transfer. At an early stage in the signaling process a signaling protein enters the nucleus and interacts directly with genes to modify expression.

Many cancer cells exhibit defects in one or more steps of signaling cascades that alter control of
cell growth, specialized cell properties, cell–cell communication, cell motility, and cell adhesion. The components of signaling pathways that are modified in tumor cells are targets for treatments that are effective and specific.

CANCER CELL BIOLOGY

Cells are the units of life. Normal cells act on each other to control their growth and other properties in balance with the entire organism. They are closely regulated by a variety of genetic and biochemical processes. For example, biological feedbacks act in much the same way that a thermostat controls heat production by a furnace. Cancer is a disease of ‘‘outlaw’’ cells, cells that have lost their normal relationship to the whole organism. A tumor originates when single normal cells mutate and develop into cancer cells, termed transformed cells. Mutations produce defects in their cellular regulatory mechanisms, changing their biochemistry and biology so that they differ from normal cells in structure and functioning and grow at the wrong times and in the wrong places.

Briefly, each cell is surrounded by a membrane that separates it from its surroundings, which include other cells, nutrients, and molecules that regulate growth and other functions. Within the cell is a fluid, cytoplasm, containing proteins and structures, including mitochondria (the source of energy for a cell , that produce chemical energy and the machinery (ribosomes) that synthesizes proteins. The nucleus, which contains the genetic material, sits in the middle of the cell. Location within a cell can determine a molecule’s possible biochemical interactions and effects. Cells of cancers develop into disorganized arrangements, and their nuclear shapes are abnormal, properties that are scrutinized carefully during diagnosis and are used to classify the stage of a cancer.

Cancer-related chromosomal aberrations

Visible changes in the structure of chromosomes in cancer cells provide direct evidence for the genetic basis of cancer. Rearrangements at many definite positions have been observed repeatedly in many types of cancers . At the molecular level are found miscoding changes, including substitutions, deletions, duplications, and rearrangements of DNA building blocks. For example, in a recent study of breast and colon cancers, 189 genes (average 11 per tumor) were frequently found to be mutated. In several cancers, mutations change the functioning of genes located at their positions. DNA is often altered in human chromosome 6 at position p21, where the cancer-related K-ras oncogene, a gene that may modify cell growth aberrantly and lead to cancer, is located. Additional copies of a particular gene make a cell resistant to the anticancer drug methotrexate. Rare cancers are produced by virus infection; for example, introduction of genetic material by the human papilloma virus causes cervical cancers. This provides further evidence for the genetic basis of cancer.