Why am I here? What is my purpose?
This blog will both serve as a good review for my cyberspace audience, and function as an organizational tool for my upcoming chalk talk!
Colon cancer is responsible for almost 650,000 deaths per year, according to the World Health Organization, and is the third most common cancer in the world. Much is being done in the laboratory to try to understand the biological mechanics behind tumor formation as well as tumor metastasis, which is when tumor cells spread to and infect organs besides the one they originated in.
In my lab, we work with the cell signaling pathway TGF-beta (Transforming growth factor-beta) and how it relates to various types of cancer. TGF-beta is involved in biological processes such as cell proliferation, cell migration, differentiation, and apoptosis (cell death) - it's pretty important. Gene targets of TGF-beta include several cell-cycle checkpoint genes, which make sure cells are correctly growing/replicating/mitosing before they can go on to the next stage - basically, they're tumor suppressors, because tumors are just unregulated cell growths. If cells don't have all the necessary components (chromosomes weren't replicated correctly, mitosis went wrong, etc), cells are stopped and can't progress and proliferate. TGF-beta helps make sure these cells are stopped. As it so happens, however, this pathway is commonly altered in human cancers. Specifically, a lot of colon cancer tumors can resist TGF-beta's checkpoint gene products, at least at first. Interestingly enough, though, in later stages of colon cancer, we find TGF-beta acting as a tumor promoter - it promotes cell motility and migration, as well as angiogenesis and immunosuppression, which are involved in tumor invasion and metastasis! TGF-beta works through its 3 receptors, TBRI, TBRII, and TBRIII, the latter of which was thought to be a redundant co-receptor but has just recently shown extreme promise. These three receptors activate kinases, which in turn direct transcription factors for many genes, some of which were mentioned above. In most cancers, TBRIII inhibits the ability of tumor cells to migrate (a loss of expression results in cancer progression), but colon cancer works in opposite ways for reasons yet unknown.
Essentially, my question is as follows: Does RIII regulate/mediate cell migration in colon cancer? Furthermore, is this ligand (TGFB and BMP) dependent? Based on what we've seen in other cancers, we would expect RIII would increase migration (since it works opposite from most cancers) and it would be ligand dependent.
