Scientists have identified a biological process that plays a key role in turning healthy cells cancerous. The long-sought sequence of chemical events may be an important factor in as many as 90% of colon cancers--one of the most common tumors among Americans--as well as numerous instances of the severe skin malignancy called melanoma.
"These are landmark findings," said Curtis C. Harris of the National Cancer Institute. In the short term, the discovery likely will make it far easier to detect potential colon cancers early, he said. In the long run, it may lead to drugs that can halt or prevent tumor formation by targeting the newly identified chemical culprits.
The same process might also be involved in other forms of cancer. That possibility is sufficiently promising that "it's worth surveying other tumor types" to see if they share common characteristics with colon cancer and melanoma cells, Harris said.
Two different research teams, reporting in three papers in today's issue of the journal Science, found that unusual activity of an otherwise obscure protein called beta-catenin is a prime reason that normal cells transform themselves into seeds of tumors.
"We believe this is the major initiating event" in the development of colon cancer, said Kenneth Kinzler of Johns Hopkins Oncology Center, a coauthor of two of the papers. "What's exciting," he said, is that "not only do we understand what is happening, but we may actually be able to do something about it."
A cell becomes cancerous when it accumulates so many errors in its genes that it ceases to behave normally. These errors, or mutations, can result from inheritance and can be caused by destructive outside agents such as radiation, toxic chemicals or viruses.
Whatever the cause, once sufficient mutations arise, a cell begins to disobey the rules that govern neighborly cohabitation among cells. It may proliferate wildly, refuse to die on the ordinary schedule for its cell type, migrate to abnormal locations, fail to migrate to proper locations, or engage in other renegade behaviors.
Presumably the transformation occurs because some genes in the cells that would ordinarily be permanently "switched off" are somehow "switched on." The studies published today indicate that the onset of that switching process is caused by changes in the customary relationship among three forbiddingly named proteins that occur normally in colon cells: beta-catenin; APC (short for adenomatous polyposis coli); and TCF/LEF (T-cell factor/lymphoid enhancer factor).
When everything is functioning right, APC grabs hold of beta-catenin and targets it for chemical disintegration. As a result, beta-catenin levels in the cell remain low. But if something goes wrong with that protection system, beta-catenin starts to build up. As it does, it binds to the TCF/LEF protein, and the pair works its way into the corkscrew spiral of DNA in the cell's nucleus.
Once there, the combined proteins activate one or more still unidentified genes that prompt the cell to run amok, apparently by sending signals to multiply unnaturally or by disabling the standard biochemical instructions that prompt routine cell death, called apoptosis.