Cancer is uncontrolled proliferation of cells

 

All living beings are made of cells that are genetically programmed to control their division and demise.

It is this orderly cell division and death that makes life possible. When the genetic program is altered to the extent that cell division is deregulated, it may make them divide faster. We call these alterations “mutations.”

Fortunately, organisms are also equipped with built-in measures (Checkpoints) to stop these cells from dividing  until they repair such defects , or in some cases, if repair is not an option, even eliminate themselves (eg: Apoptosis). But unfortunately these measures are not totally fool proof. When these mechanisms fail, the result is uncontrolled cell division and spread - also known as Cancer.

Did you know there are programs that help cells clean up their waste and do some of the regular house keeping jobs?. For example, Autophagy is a genetically regulated garbage disposal program that performs this function by collecting the waste in tiny garbage bags called “autophagosomes” and carrying them to lysosomes where they are degraded.  This process helps cells recycle unwanted organelles to generate energy during starvation to support survival.  Our initial findings showed that this is an important pathway that prevents tumorigenesis by limiting necrotic cell death and inflammation (Degenhardt K., Mathew R. et al., Cancer Cell 2006) 

In 2007 we provided the first evidence that this process functions to limit chromosomal instability, one of the causes of Cancer (Robin Mathew et al., Genes & Dev., 2007; Highlighted in  Nature Genetics and Nature Reviews Cancer), providing the first molecular explanation for how autophagy prevents Cancer.

Our latest finding which appears in June 12th (2009) issue of the journal Cell, shows that this garbage disposal pathway functions as a tumor suppressor mechanism at least in part, by limiting persistent accumulation of a protein called p62/SQSTM1 (Mathew et al., Cell 2009 & Cell featured leading edge mini review by Jorge Moscat). Cells accumulate damaged proteins under metabolic stress, which induces autophagy to eliminate this toxic cellular garbage by lysosomal degradation.  The protein p62/SQSTM1 serves as the garbage man of the cell by collecting and delivering the damaged proteins to autophagosomes, which then fuse with lysosomes where p62 itself is degraded along with the cargo.  In cells defective for autophagy, this process is impaired resulting in the accumulation of p62 and p62-containing protein aggregates leading to oxidative stress and tumorigenesis.

 

How do these mechanisms work? How are these defects identified and repaired? How and why do they fail? What can we as humans do to prevent or even reverse these defects? These are some of the questions that we ask ourselves in the lab (Robin Mathew et al., Nature Reviews Cancer, 2007).

 

We are devoted to studying these mechanisms right within the cells. We try to find answers to these questions by designing and performing elegant experiments within living cells. Then we test them in animal models and eventually in human beings. This is what enables us to expand our understanding of the disease. This understanding of the disease is the key to the development of new and more effective drugs and strategies to treat the disease.

Today’s research is tomorrow’s treatment, just as today’s treatment was yesterday’s research.