In many respects, cancer is like a complex software program of life that has got out of control; instead of the code for normal cells, a code for making abnormal cells is executed. Now, a new study in Nature Cell Biology suggests there may be a way to change the code so that cancer cells revert back to normal cells.
Senior investigator Panos Anastasiadis, a professor of cancer biology at the Mayo Clinic in Jacksonville, FL, says their findings represent "an unexpected new biology that provides the code, the software for turning off cancer."
The discovery centers around the role of adhesion proteins - the glue that keeps cells together to form tissue - and how they interact with microRNAs (miRNAs) - molecules that orchestrate cell programs by regulating gene expression.
The study shows that when normal cells come together, a specific group of miRNAs suppresses genes that encourage cell growth. But, for some reason, this is disrupted in tumor cells, and growth becomes uncontrolled - the hallmark of cancer.
The researchers found when they restored normal miRNA signals in cancer cells, they could reverse the process so growth did not get out of control.
The team became interested in the problem when they tried to reconcile conflicting results that were coming to light about two adhesion proteins: E-cadherin and p120 catenin.
These adhesion proteins are important for normal tissue formation, and for a long time were thought to be tumor suppressors.
The molecules have a 'good face' and a 'bad face'
However, the team began to question the assumptions surrounding E-cadherin and p120 catenin because both molecules are found in tumor cells and appear to be important for tumor growth too.
Prof. Anastasiadis says that led them to wonder if the molecules " have two faces" - a "good one" that helps keep normal cells behaving correctly and a "bad one" that drives tumor growth.
During their research, the team discovered this seems to be the case, but were no wiser about why. It was not until they studied a new protein - called PLEKHA7 - that associates with E-cadherin and p120 that they found the answer.
They found that the new protein is essential for ensuring E-cadherin and p120 maintain their "good face" and stick to their tumor suppression role.
The researchers say that when PLEKHA7 is lost, the adhesion complex that ensures E-cadherin and p120 keep their "good face" on is disrupted, the miRNAs become misregulated, and E-cadherin and p120 switch to their "bad face" and become tumor-promoting.
Prof. Anastasiadis says they believe this is an "early and somewhat universal event in cancer." In the vast majority of human tumor samples they looked at, they found the adhesion complex was missing, while E-cadherin and p120 were still present.
He notes this is like a speeding car that has a lot of gas (E-cadherin and p120) but no brakes (the PLEKHA7 complex), and concludes:
"By administering the affected miRNAs in cancer cells to restore their normal levels, we should be able to re-establish the brakes and restore normal cell function. Initial experiments in some aggressive types of cancer are indeed very promising."
The study brings together two fields of biology - cell-to-cell adhesion and miRNA biology - that until now, have not normally worked together. Lead author Dr. Antonis Kourtidis, a researcher in Prof. Anastasiadis' lab, comments on the result:
"Most significantly, it uncovers a new strategy for cancer therapy."
In the following video, Prof. Anastasiadis describes the work that went into the study:
Meanwhile, Medical News Today recently learned how researchers at the University of Freiburg in Germany discovered that migrating cancer cells alter bone tissue to form tumors. The researchers found that migrating cancer cells produce a protein called cathepsin K that appears to help them survive, and possibly even thrive, in bone tissue.