Cancer Cell Signaling Proteins Provide Link to Conquering Tumors Through Nutrition

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Metabolic schematic of glycolysis, a core cellular energy producing pathway implicated in cell growth and cell signalling. Source: Wikipedia user Thomas Shafee [Licensed under CC BY 4.0].

Metabolic schematic of glycolysis, a core cellular energy producing pathway implicated in cell growth and cell signalling. Source: Wikipedia user Thomas Shafee [Licensed under CC BY 4.0].
In a groundbreaking study published in Nature, researchers have proposed that the nutrient uptake profiles of mammalian cells can be used to determine whether these cells are at risk for becoming cancerous.1 This research joins prior research linking cellular metabolic processes with the chance of cancer and underscores the importance of building a greater understanding of cellular nutrient uptake.2

Like other prior research, the new research identifies cellular signaling as the critical factor in detecting oncogenesis via nutrient uptake.3 If researchers want to take a stab at building a metabolic and nutrient uptake profile that can be used diagnostically to predict cancer development and progression, they’ll need powerful data tracking software to help build data sets of normal behavior to compare with cells at risk.

Is Nutrient Uptake Really A Critical Aspect Of Malignancy?

At first glance, the new research may seem like a bit of a no-brainer. It’s obvious that cancer cells require nutrients in order to grow, and it isn’t hard to believe that they’d need a different cellular signaling environment to direct them to uptake more nutrients than a normal cell in order to fuel their abnormal growth and endless division.4 Where most biologists may fail to make the connection with the relevance of the new research is on a subtle point that’s more medicine than laboratory science: local nutrient imbalances caused by cancer cell nutrient uptake are multimodal, don’t necessarily consume nutrients that a healthy cell might, all while depriving healthy cells of their needed fuel.5

The fact that cancerous cells consume nutrients that healthy cells don’t is important because it means healthy cells are subject to an environment that contains ever-increasing byproducts of the cancer cells’ metabolism which they wouldn’t have to tolerate otherwise.6 These metabolites may suppress healthy cells while also acting as cellular signaling molecules and egging on cancer cells to accelerate their growth, making them particularly important.7

As the cancerous cells voraciously devour all kinds of nutrients, local healthy cells grow weaker for lack of nutrients to call their own and for unfamiliar and detrimental metabolite buildup, causing the nearby, rapidly growing cancer cells to easily displace them. Though outright cell death of the healthy cells isn’t likely, their steadily weakening state contributes heavily to loss of tissue function and many of the symptoms associated with cancer. Thus, the new research is one more piece of the puzzle which describes generalized cellular level cancer pathology.

What Might It Take To Manipulate Cancer Cell Nutrient Uptake Signaling?

As noted in the new research, cancer cells seem to be triggered to uptake nutrients by cellular signals that are present during cellular proliferation in healthy cells. Independent of “normal” growth mechanisms, cancer cells also receive cellular signals which prompt them to enter a “survival mode” where the type of nutrient absorbed is less important than merely absorbing as many nutrients as possible. This means that cancerous cells will voraciously consume as many nutrients as it can, using any metabolic breakdown pathways the cell is capable of to convert those nutrients to energy. If researchers want to understand this phenomenon more to potentially interrupt it or use it as a diagnostic test, they’ll have to:

  • Identify the rate of healthy cell nutrient consumption while quiescent and while proliferating
  • Identify the rate of healthy cell nutrient consumption after a period of starvation
  • Identify the metabolites excreted by healthy cells under conditions of quiescence, proliferation, and post-starvation nutrient uptake
  • Track the transcriptome of healthy cells during each of the above nutrient uptake and metabolism profiles
  • Characterize the rate of cancer cell nutrient consumption in addition to the library of nutrients and metabolites used and produced
  • Characterize the effect of cancer cell metabolites on healthy cell nutrient consumption in all states
  • Track the transcriptome of the cancer cells and the healthy cells while exposed to cancer cell metabolites
  • Track the transcriptome of cancer cells and healthy cells while starved of nutrients to see if they are the same
  • Identify which cellular signals are transcribed in cancer cells during proliferation but not in healthy cells

Once researchers have a handle on these data, managing the information will be the next challenge. Most of the experiments required to flesh out the above questions will be performed in model cell lines, which are notoriously difficult to compare to living human cells from a donor with an unknown genome. After gathering basic data from tumor cell lines, it’ll be important to test preliminary hypotheses against fresh human cells prompted to turn cancerous using known methods. While these experiments will only be able to shed light on a tiny piece of the problem–the initial cellular signaling traces of cancer–it’s easy to imagine that a relatively simple diagnostic test could be developed after only a few experiments exploring nutrient uptake. For rare cancers, a simple nutrient and cell signaling test could be a lifesaver.

Quantifying The Diet Of Cancer Cells

Each nutrient, metabolite, and signaling molecule will need a corresponding data set for each experiment before any kind of conclusions can be made from the data. Genetic data and metadata also pose substantial issues, as the change of nutrients and metabolites over time could potentially be extremely granular. Researchers will need a powerful information technology platform that can follow them to the level of detail required to answer these data rich questions and start to create interventions targeting cancer cell nutrient uptake signaling molecules.

Pipeline Pilot  gives you the building blocks to create data science solutions and make them available to be used strategically. Users of any programming level can quickly create custom protocols for a variety of applications. Using Pipeline Pilot, managing the metadata, experimental planning, nutrient profiles, and granular data of metabolite concentrations will be quick and easy. Contact us today to find out how we can help you design the cell signaling targeted therapeutics of the future.

  1. “Nutrient Acquisition Strategies of Mammalian Cells.” April 2017, https://www.nature.com/nature/journal/v546/n7657/full/nature22379.html
  2. “Links Between Metabolism and Cancer.” 2012, http://genesdev.cshlp.org/content/26/9/877.full
  3. “Role Of Nutrients And mTOR Signaling In The REgulation Of Pancreatic Progenitors Development.” June 2017, http://www.sciencedirect.com/science/article/pii/S2212877816303131.
  4. “Nutrient-Sensing Mechanisms Across Evolution.” February 2015, http://www.cell.com/cell/fulltext/S0092-8674(15)00242-1?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867415002421%3Fshowall%3Dtrue
  5. “The Emerging Hallmarks of Cancer Metabolism.” 2016, http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink&action=reflink&origin=npg&version=1.0&coi=1:CAS:528:DC%2BC28XjtFSrtw%3D%3D&pissn=0028-0836&pyear=2017&md5=042d80ee3bdd8817e1b0a6c072e6d7e7
  6.  “Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation.” May 2009, http://science.sciencemag.org/content/324/5930/1029.long
  7.  “Regulation Of Cancer Cell Metabolism.” February 2011, https://www.nature.com/nrc/journal/v11/n2/full/nrc2981.html