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Kevin Shimkus, B.S.


In muscle research, we tend to pay a great deal of attention to a particular signaling protein called mTOR, a key regulatory protein that signals for cell growth through the creation of new proteins. Consider protein building similar to a race car. The larger the engine, the greater potential for speed. Similarly, the more mTOR protein present in any given cell, the greater potential for more protein construction. And just like the gas pedal fuels the engine, mTOR is a signaling protein, and can be various levels of active (like a pedal’s ability to regulate speed). If a number of different processes all signal for ‘Go’, then the cell builds as much protein as it can, as quickly as it can. So just as a souped-up car takes off rapidly, a muscle cell can signal for tremendous muscle growth very quickly, given the right conditions.

Here’s where muscle research gets very tricky. In an ideal situation, if given the option for more muscle mass, many people would take that offer. A great deal of muscle research is aimed at upregulating (increasing) mTOR’s signal, which allows for more muscle protein synthesis. Exercise, nutrition, and a number of endocrine factors all increase mTOR signaling and contribute to muscle production. Potentially,pharmaceuticals that focus on mTOR could provide even larger muscle gains. The reason researchers haven’t yet accomplished this is wariness of a major concern: cancer.

Cancerous tumors are the jet-fueled F1 Race Car of the cell world. They’re designed to grow as fast and as large as possible, and they rely on mTOR signaling to build proteins, just like normal and healthy muscle cells. So this presents a very troubling problem for researchers: if we’re not careful, a muscle-growing therapy for people could put them at a higher risk of developing rapid and serious cancers. So while we have been trying to build bigger, faster race cars, cancer researchers are trying to build smaller, slower cells. A lot of cancer research is based around slowing down and minimizing mTOR activity in tumor cells (the exact opposite goal of muscle research).

This doesn’t necessarily doom muscle research to causing cancers and ruining medical science. As mentioned before, numerous other proteins and factors come into play, and some may respond different in muscle cells than in cancerous cells. A great deal of information from cancer research can help muscle research, and vice versa. Gaining a better understanding of mTOR and other signaling proteins, and learning the safe and appropriate ways to manipulate them can ultimately allow us to improve cancer research AND learn to improve muscle-building therapies. This gives you a nice, big, fast race car that won’t bring any problems along.


References

  1. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM: DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival. Cell 2009, 137(5):873-886. http://ac.els-cdn.com/S0092867409003894/1-s2.0-S0092867409003894-main.pdf?_tid=85c9f47e-f733-11e3-b299-00000aab0f26&acdnat=1403128821_122f0307f93324c9236015a2697e1805
  2. Zhao Y, Xiong X, Sun Y: DEPTOR, an mTOR Inhibitor, Is a Physiological Substrate of SCFβTrCP E3 Ubiquitin Ligase and Regulates Survival and Autophagy. Molecular Cell 2011, 44(2):304-316. http://ac.els-cdn.com/S1097276511007192/1-s2.0-S1097276511007192-main.pdf?_tid=9ce4ce5e-f733-11e3-9831-00000aab0f26&acdnat=1403128859_9c61ed65cefb5a6f23e2a0ebee2f6ff4
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  4. Proud CG: Dynamic Balancing: DEPTOR Tips the Scales. Journal of Molecular Cell Biology 2009, 1(2):61-63. http://jmcb.oxfordjournals.org/content/1/2/61.full.pdf+html
  5. Shimkus KL, Wudeck EV, Shirazi-Fard Y, Nilsson MI, Greene NP, Hogan HA, Fluckey JD: DEPTOR Expression Correlates with Muscle Protein Synthesis. International Journal of Exercise Science: Conference Proceedings 2013, 7(5):Article 7. http://digitalcommons.wku.edu/cgi/viewcontent.cgi?article=1618&context=ijesab
  6. Nilsson MI, Dobson JP, Greene NP, Wiggs MP, Shimkus KL, Wudeck EV, Davis AR, Laureano ML, Fluckey JD: Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. The FASEB Journal 2013. http://www.fasebj.org/content/27/10/3905.full.pdf+html
  • Understanding mTOR: Great for Muscle, Bad for Cancer


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