CELL IN CANCER MODE

In a normal cell, things are operating normally.  The cell feeds itself and uses energy to allow its normal functions to unfold, and knowing that hard times will come to it, it even puts some energy aside for reserve. When one looks at Mitochondrial activity, one will find Gluconeogensis in full display.  This Normal Metabolism that some have called NORMAL CELLULAR MODE tends to show anabolism and normal oxygen.  In clear Hypoxic conditions which are read by the cell as a stress, there is the reversal of the chemical reactions as catabolism ensue and Fatty Acid become the source of energy and Glycolysis enters into play.   Under these circumstances, which can occur in normal life, catabolism is accompanied with Glycolysis.

In 1920, Walburg described the Walburg effect which characterizes the CANCER CELL MODE.
Indeed in cancer there is a dissociation of Glycolysis and with Catabolism.  In Cancer mode, the cell adopts Glycolysis and Anabolism.  Glycolysis is to escape the normal requirements of constant feeding, be in a stress like while Making new proteins (Anabolism) to allow cell division and proliferation.  One hundred years after the Walburg effect was described, it is now molecularly explained by Researchers.  Indeed, to do this the cell induces a genetic controlled hypoxia  by suppressing SIRT3 which overexpresses HIF.  This induces Hypoxic conditions in the Mitochondria.

http://onlinedigeditions.com/publication/?i=104782&p=12

The Cancer mode can now be measured
but quantifying:
1 Pyruvate Dehydrogenase kinase
2. Over-expression of GLUT1
3. level of vascular endothelial growth factor
4. level of suppression of SIRT3 and related  Increase in ROS1
5. level of HK2, IDH, and SOD3

and if you are very smart, start by including c-JUN, HIF, Myc and TCA (fatty acid)

And as you progress with the clues given you will understand why overexpression of ROS1 could predict resistance to MTOR Inhibitors.   And I believe it predicts of low participation of MAPK as a driver of pathogenesis therefore decreasing the value of MTOR inhibitors.  more detail to come.

ANOTHER WAY OF INDUCING HIF:
"Description

Dimethyloxaloylglycine (DMOG) is an inhibitor of PHF (prolyl hydroxylase, PHD) and asparaginyl hydroxylase FIH-1 (Factor inhibiting HIF, FIH). DMOG has been observed to upregulate HIF (hypoxia stabilize) HIF-1α at specific concentrations. In HMEC-1 cells DMOG attenuated REF-1 (redox factor 1) through activation of HIF. PHT cells exposed to DMOG were observed to upregulate the FSTL3 (follistatin-like 3) transcript. Attenuation of myocardial injury by DMOG was demonstrated in the rabbit ischemia reperfusion model. In NGF deprived neurons DMOG increased cell survival through inhibition of cytochrome c release." SOURCE

 santa cruz biotechnology, inc.

PLEASE DON'T TAKE DMOG WITHOUT BEING IN A CLINICAL TRIAL!  (CRBCM OPINION PROTECTED BY THE FIRST AMENDMENT!)