Treating Colon Tumors

Through study findings published Friday in Cell Reports, a team of scientists at VCU Massey Cancer Center discovered a previously unknown interaction between proteins that is responsible for supplying energy to tumor cells and could hold significant implications for the development of future treatments for colon cancer.

The potential answer lies within a class of fatty compounds known as ceramides. Ceramides regulate a number of vital cellular functions, and many cancer drugs stimulate ceramide generation to help fend off disease. When that production of ceramide is cut off, cancer cells can survive and grow more efficiently.

Senkal and his team began extensively screening cells in the lab to identify what proteins regularly interact with ceramide-producing proteins to identify potential patterns that could warrant further investigation.

Ceramide synthases — the enzymes responsible for the generation of ceramide — come in a variety pack of six different flavors: Ceramide synthase 1-6.

Through their research, Senkal’s team observed that the first flavor, ceramide synthase 1 (CerS1), was highly interactive with a particular protein known as heat shock protein 27 (Hsp27). Heat shock proteins act like chaperones for other proteins to retain their full function; however, an overabundance of them can tip the scales and prevent ceramide synthases from doing their job.

Through the study, they identified a specific biological mechanism through which Hsp27 interacted with and inhibited the function of CerS1 in colon cancer cells. By deliberately blocking the activity of Hsp27 in these cells, the researchers confirmed the decreased presence of Hsp27 led to a heightened reactivation of CerS1, which in turn forced a reduction in mitochondrial function.

“Cancer cells rely on mitochondria to have the energy to multiply. Without it, the cancer cells can no longer sustain the amount of energy they need and die,” Senkal said.

By blocking the function of these heat shock proteins, they were essentially able to reactivate the cellular hand that could pull the plug on the power source connected to the cancer, Senkal said.

This revelation led the study authors to suggest that Hsp27 could be a primary target in the creation of novel therapies for colon cancer.

Although this study showed encouraging results in colon cancer, they hope to broaden the scope of this research to additional solid tumors in which the overexpression of Hsp27 has been observed, including lung, pancreatic and prostate cancers.

Sources:

Rowan A. Boyd, Saurav Majumder, Johnny Stiban, Grace Mavodza, Alexandra J. Straus, Sachin K. Kempelingaiah, Varun Reddy, Yusuf A. Hannun, Lina M. Obeid, Can E. Senkal. The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation. Cell Reports, 2023; 113081 DOI: 10.1016/j.celrep.2023.113081

Virginia Commonwealth University. (2023, September 12). Blocking proteins could pull the plug on power for colon tumors. ScienceDaily. Retrieved September 13, 2023 from www.sciencedaily.com/releases/2023/09/230912165650.htm

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