Pathways to Cancer

A signaling pathway begins with the arrival of a chemical signal — such as a hormone or growth factor — at the cell surface. The gray structures sticking out of the cell membrane are receptors for these incoming signals. The signal, in this case a platelet-derived growth factor (here in purple and blue), encounters and binds to its matching receptor. A second receptor protein joins in, making the growth factor fit like a key in a lock. The binding of the growth factor causes the receptors to change shape. This change in the protein will be conducted through the membrane and into the cell’s interior — the cytoplasm.

The signal is conducted through the cell membrane, into the cytoplasm. The binding of the growth factor outside the cell has caused the ends of the receptor (in gray) to intertwine and activate each other (shown as yellow flashes of light). Once active, the modified receptor ends interact with messenger proteins that will carry the signal through the cytoplasm.

From our position in the cell’s cytoplasm, we can see the ends of the receptor (in gray) being drawn together as the growth factor outside the cell binds. The receptor ends activate each other before binding an adaptor molecule (shown in pink) and an exchange factor (shown in light purple). An important protein in this pathway, known as Ras (shown in red) then swings around to be activated. Ras, in turn, activates three white “Raf” proteins, before another protein (shown in blue) moves in to deactivate it. Ras is a key “switch” in this pathway — mutations in the ras gene and protein are common in cancer cells.

Many signaling pathways ultimately pass messages to the nucleus of a cell. The Raf protein (shown in white) activates another messenger protein (in brown) as it passes through fibers that make up the cell’s cytoskeleton. The signal is passed to yet another messenger (in purple). These messenger proteins are known as kinases, enzymes with the ability to activate other proteins through the addition of phosphate groups. This protein travels to the nucleus past cellular organelles such as the mitochondria (in glowing orange) and the network of membranes known as the endoplasmic reticulum (shown in light brown).

The activated protein (in pink) is transported into the nucleus through a pore in the nuclear membrane. The nucleus contains tightly wound coils of DNA (shown in green). The signal is passed to two other molecules, Fos and Jun (in yellow and pink) that team up to locate a specific gene along the DNA. Fos and jun bind the DNA, starting the process of transcription. Other proteins are then called into play that unwind and open the DNA molecule so that RNA polymerase (shown in brown) can make a copy of the genetic information. The “copy,” called messenger RNA (here in light green), is packaged with a set of carrier proteins and leaves the nucleus. The cell will use this copy to make a new protein.

In the cytoplasm, the messenger RNA is released from its carrier proteins and binds to a protein assembly complex called a ribosome (the multicolored structure). This begins a process called translation, where the ribosome reads the information encoded in the RNA and assembles a protein from amino acids found in the cell. Many ribosomes can operate at the same time to make multiple copies of the protein. The ribosomes are anchored on the outer membrane of the endoplasmic reticulum. If you look carefully, you can see the ghostly shapes of the newly made proteins accumulating on the inner side of the membrane. Once the job is done, the ribosomes and RNA part company.

The newly made proteins leave the endoplasmic reticulum wrapped in a layer of membrane called a vesicle. They travel toward the Golgi apparatus (on the right) where the proteins are modified and sorted for transport. The Golgi is busy with protein traffic moving in and out. The vesicle fuses with the membrane at one end of the Golgi and a new vesicle containing the modified proteins is pinched off the other side. The proteins are transported through the cytoplasm and delivered to where they are needed. Some proteins are used inside the cell. Others, like these growth factors, must be exported to function. The vesicle fuses with the cell membrane, dumping the proteins outside the cell. The released proteins will signal surrounding cells, or, in some pathways to cancer, will coax this cell into further action.