Data from: Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma

Among the numerous changes associated with the transformation to cancer,
cellular metabolism is one of the first discovered and most prominent.
However, despite the knowledge that nearly every cancer is associated with
the strong upregulation of various metabolic pathways, there has yet to be
much clinical progress on the treatment of cancer by targeting a single
metabolic enzyme directly. We previously showed that inhibition of
glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells
of origin had no effect on the initiation or progression of cutaneous
squamous cell carcinoma, suggesting that these cancers are metabolically
flexible enough to produce the necessary metabolites required for
sustained growth in the absence of glycolysis.  Here we focused
on glutaminolysis, another metabolic pathway frequently implicated as
important for tumorigenesis in correlative studies. We genetically blocked
glutaminolysis through glutaminase (GLS) deletion in cancer cells of
origin, and found that this had little effect on tumorigenesis, similar to
what we previously showed for blocking glycolysis. Tumors with genetic
deletion of glutaminolysis instead upregulated lactate consumption and
utilization for the TCA cycle, providing further evidence of metabolic
flexibility. We also found that the metabolic flexibility observed upon
inhibition of glycolysis, pyruvate oxidation, or glutaminolysis is due to
post-transcriptional changes in the levels of plasma membrane lactate,
glucose, and glutamine transporters. To define the limits of metabolic
flexibility in cancer initiating hair follicle stem cells, we genetically
blocked both glycolysis and glutaminolysis simultaneously and found that
frank carcinoma was not compatible with abrogation of both of these carbon
utilization pathways.  These data point towards metabolic
flexibility mediated by regulation of nutrient consumption, and suggest
that treatment of cancer through metabolic manipulation will require
multiple interventions on distinct pathways.