The Crux of Tumorgenesis

The secret of cancer proliferation and persistence lays in phenomena at the membrane, where the NOTCH, Wnt and Hedgehog are located.  These functions of the membrane start and drive the cancer with help from the ABCG2, MRp1, Pgp gene;  it gives it resistance to powerful medications (Adriamycin, CPT11), with SuFu/PEX it reaches a gene capable of inducing malformation, with FOXM1, proliferation is guaranteed, through GLI1, Cyclin D2 is reached. Differentiation is reached though the MEK and failure of control is assured by dysregulation at the FAK.  The Cancer's mind set is driven by the FOXM1 for sure.  Other genes involve the NANOG, the PTCH1, The SOX and the OCT, CDH1, Shh,Twist, Plakoglobulin...

AMAZING GLYCOCALYX
CELL SUGAR COATING!

One of the wonders of the cell is its sugar coating.  Indeed this fine layer of mostly sugar component serves many functions to the cell.  From adhesion to other cells to providing signals to the surrounding milieu.  It is given to that sugar coating the responsibility to find the cell location in our tissues during global positioning in the embryo, sperm locating of the egg to fertilize, and recognition of bacteria passing by in the blood.
Glycocalyx, the sugar coat of the cell, plays a major role in cancer, it is one of the ways the immune system recognizes the early change of a normal cell to a cancer cell.  If changes in Glycocalyx are not striking enough to be noticed by our immune surveillance, cancer will be allowed to survive.  The other change of course involves the receptors on the cellular membranes.
How well our immune system detects the change depends on the status of that immune system, and how big of a change has occurred to the Glycocalyx as a result of malignant transformation.  Studying the changes in receptors and Glycocalyx can help us locate and selectively hit the cancer cell while sparing the normal cell.
Sugar coating glycocalyx !

FLIPPASE, FLOPPASE, SCRAMBLASE

One of nature's secret and ability to hide it, is by being simple.  While we expect things to be complicated and full of contorsions,  we are startled when at the end what we find is simple to understand!  One of the things we had figured out to be simple is the role of flippase and floppase, and may be the role of scramblase.   If one looks at a battery we use to power small electric equipment, one side is positive, the other is negative.  So there is a positive pole and a negative pole.  We can conclude that the battery is polarized.  The limit of a cell or one way the cell keeps what is inside of it, is by having its membrane polarized like an electrical fence.  The cell has understood that to be electrically polarized you got to have molecules in the membranes full of electrons.   And these electron-filled-molecules need to be maintained in position no matter what !  So the cell figures we need some Flippases and floppases to put things in the order above.  Meaning if the molecules we need in position A is outside the cell in position B, flip it in the right position A no matter what.  While flippase go A to B bringing these molecule inside.  Floppase goes B to A, sending molecule outside.  The Scramblase does both functions to mix things up!

This seems simple enough but wait!
This is how the cell tells the other cell "I am a dead cell, get rid of me"
Indeed, dead cells move Phosphatidyl serine, a normally internal surface molecule, to the outside of the cell, making it one of the most powerful signals to the Macrophage that this cell needs to be attacked and removed.
This disruption in lipid molecules is also linked to Bleb formation in the membrane, another powerful sign of cell death.   It is related to Caspase activity as an inducer of death, and therefore it is related to our 2nd law of nature which induces Caspases.  YOU CAN SEE HOW SIMPLE THINGS GET COMPLICATED FAST!  (This is also linked to protein Kinase activation, by the way!)
QUESTION NOW: ARE FLIPPASE AND SCRAMBLASE TARGET FOR THERAPY?  You better believe it.

We are working hard at CRBCM, but CPRIT is resisting with the help!  Please help us!

NOTE   A is inside the cell
              B is outside the Cell, in our example.