Colon cancer’s cellular crossroads
Colon cancer development and progression involves alterations in several cell signaling pathways. Activation of the Wnt pathway is involved in the early stages of tumor development, while inactivation of signaling through the TGF-beta pathway (which typically suppresses tumor formation) is involved in later stages. However, the interactions between these pathways remain unclear.
R. Daniel Beauchamp, M.D., and colleagues investigated these interactions in human colorectal cancer samples, cell lines, and a mouse model of colon cancer. In a study published in the March issue of Gastroenterology, they show that reduced levels of Smad4 (a component of the TGF-beta pathway) correlated with increased levels of beta-catenin (a Wnt pathway component) in human colon cancers. In cell lines, depletion of Smad4 also increased beta-catenin and Wnt signaling. Similar interactions were found in intestinal tumors of mice.
The findings provide important information about the interaction among these signaling pathways, which could aid in assessing prognosis and identifying new therapeutic targets for colorectal cancer.
The research was supported by grants from the National Cancer Institute, the National Institute of General Medical Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources of the National Institutes of Health.
— Melissa Marino
iPOND method goes fishing for proteins
(iStockphoto.com)
Now, David Cortez, Ph.D., and colleagues have developed a procedure to isolate proteins on nascent DNA (iPOND). Their method, described in the March issue of Nature Protocols, can be applied to any proliferating cell type. It relies on the incorporation of a chemical “label” into newly synthesized DNA. The label can be modified by a chemistry reaction, and proteins linked to the DNA can be isolated and characterized.
The researchers have used the iPOND technique to identify proteins associated with active replication forks, to monitor changes in chromatin located various distances from the replication fork, and to detect proteins or modifications of proteins at damaged replication forks.
This research was supported by grants from the National Cancer Institute of the National Institutes of Health and by the Department of Defense Breast Cancer Research Program.
— Leigh MacMillan
Obesity turns “good” cholesterol bad
Obesity-linked changes in the function of HDL – the “good” cholesterol – may increase the risk of coronary heart disease, but how obesity impairs HDL function is not well defined.
(iStockphoto.com)
John Stafford, M.D., Ph.D., and colleagues studied HDL composition in transgenic mice expressing CETP, a triglyceride-cholesterol shuttle protein that regulates HDL composition but is normally absent in mice. They report that after ovariectomy (to induce menopause and its associated metabolic changes), CETP mice fed a high-fat diet had accelerated weight gain and impaired glucose tolerance compared to those fed a low-fat diet. The high-fat diet also changed HDL composition, increasing levels of proteins involved in triglyceride metabolism.
The findings, reported in the March Journal of Lipid Research, suggest that the absence of ovarian hormones negatively impacts the response to a high-fat diet in terms of glucose tolerance and HDL composition. The studies also suggest that the CETP mice may be a useful model for defining how metabolic changes affect HDL composition and function.
This research was supported by the Department of Veterans Affairs, the American Heart Association, Atlantic Philanthropies, Inc., the American Diabetes Association, the John A. Hartford Foundation, and the Association of Specialty Professors. The National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute of the National Institutes of Health also supported the studies.
— Leigh MacMillan
Smoking stokes cells’ cancer capacity
Smoking contributes to the vast majority (around 85 percent) of lung cancer cases. The TGF-beta signaling pathway – which regulates cell growth and proliferation – is altered in several cancer types, but little is known about how smoking affects this pathway.
(iStockphoto.com)
To investigate this, Debangshu Samanta, Pran Datta, Ph.D., and colleagues exposed human lung epithelial cells (cells that line the airways) and lung cancer cells to low doses of “cigarette smoke condensate,” or “CSC,” for nearly one year.
They found that chronic CSC exposure decreased expression of Smad3 (a component of the TGF-beta pathway), reduced cell death, increased cell viability and enhanced tumor-forming capacity. These effects could be reversed by replacing Smad3 or withdrawing CSC. In human tumors, Smad3 expression was lower in those of current smokers compared to tumors of never-smokers.
The study, featured on the cover of the March Cancer Prevention Research, suggests that the decrease in Smad3 expression may represent a potential biomarker for smoking-induced lung cancer risk.
The research was supported by grants from the National Cancer Institute of the National Institutes of Health and the Department of Veterans Affairs.
— Melissa Marino
We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
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