We’ve been providing a fair bit of coverage on cancer recently, and today will be no exception.
Unfortunately, right now I can offer little more than a pointer to the research article (published in The Journal of Clinical Investigation). I’m still working my way through it and may not have the time to return. So if you’re interested in sharing your thoughts on it, please add to the comments below!
Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways.
The signaling mechanisms triggered by glucose metabolism have been widely investigated ina number of diseases, such as diabetes. There is also ample evidence — starting with Warburg’s findings(2) — that tumors require more aerobic glycolysis and more recently, that oncogenic pathways will increase glucose uptake and metabolism, interpreted as a necessary step for increased growth and increased energy production for tumors(6-8). The reverse (i.e., a direct causative role of increased glucose uptake and its relation to metabolic patterns) was originally reported in chick embryo fibroblasts and their RSV-transformed counterparts more than 3 decades ago, as discussed above. We believe ours is the first mechanistic study to shed light on how a breakdown in homeostasis of sugar uptake and its metabolic signalign could be instrumental in malignant progression.
[…]
Our findings provide a hitherto-undescribed direct role of increased aerobic glycolysis in inducing he cancer phenotype, in which increased glycolytic activity regulates the canonical oncogenic pathways dynamically and reciprocally. These results may provide additional evidence for how hyperglycemia in diseases such as obesity and diabetes could provide a microenvironment that results in higher risk of some cancers (69.70). Additionally, our findings may explain how small molecules, such as metformin (used for treatment of diabetes and known to lower blood glucose levels), decrease the risk and mortality of several types of cancers (69,71). (source)
Ironically, these facts are rarely here of this “treatment” as opposed to chemotherapy, radiation & surgery. Keep up the good research.
Many thanks, Michael, for this seminal paper on sugar and oncogenesis. An excellent article on the life and scientific philosophy of Dr. Mina Bissell is a must read for anyone concerned about understanding cancer and its treatment. The article can be found in the December 2007 issue of East Bay Express (http://www.lbl.gov/LBL-Programs/lifesciences/BissellLab/minapersonal/2008%20awards/East%20Bay%20Express%2012-12-07.pdf)
A brief quote: “A crucial part of cancer formation, Bissell believes, is not just what goes wrong inside the cell, but what goes wrong in the way it interacts with its extracellular matrix, the 3-D architecture that surrounds and supports the cell. If Bissell is right, her insight will revolutionize not only how cancer is understood and treated, but perhaps even what it means to have the disease. She champions a startling idea: that cancers can be reversed. ”
Note especially “[it] is not just what goes wrong inside the cell, but what goes wrong in the way it interacts with its extracellular matrix…” This is an area that begs for greater understanding.
Hi Michael,
Very nice find. Interesting on many fronts. The need for 3D structured culture to get a revertible phenotype is very interesting. Alfred’s link to the information that Dr Bissell is thinking about matrix conditions possibly means that the role of the fibroblast will become progressively more important as cells which modify the environment around cancer cells. It is difficult to overemphasise how important fibroblast patterns are to oncologists looking at field neoplasia in fixed tissues when trying to predict their behaviour. Perhaps new models will need to be 3D with accessory fibroblasts????
I’m hoping to get to look at her pathways to see if there is any way of teasing out the cytoplasmic effects on redox status and whether there is any information on mitochondrial status in the little snippets about oxygen consumption under elevated glucose, normal glucose and 2-deoxyglucose. Especially if she compared normal to neoplastic and reverted cell cultures or if this can be extracted from the results section.
There is a lot of work in trying to get your head round a novel approach with potential insights!
Thanks for the find.
Peter