Speculations on DPC4 gene!

 "The K-ras oncogene is activated in approximately 90% of pancreatic adenocarcinomas, and the DPC4 (MADH4/SMAD4) tumor suppressor gene is inactivated in approximately 55% of pancreatic adenocarcinomas." McCarthy et al.
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Another functional Misnomer the DPC4 gene
It is a growth factor that stops proliferation (GROWTH FACTOR THAT INHIBITS IT!)
It is one of these things that nature has created to balance its growth.   And when the breaks are absent, proliferation of cells will go wild.  I suspect it is one of the genes that comes into effect early at the end of embryogenesis when tissue differentiation has to end.  It got to have links to the NOTCH to be so powerful a gene!  With the NOTCH, this will explain how so determined cancer induced by this deletion will stubbornly progress thinking it is doing the right thing!  NOTCH is the guy that convince cells to agree to the mission! Coupling the determination of the NOTCH with removing break to proliferation makes for one deadly disease!  The cells don't know the mission is destructive!  The KRAS amplification is also a result of removal of breaks!  Indeed reports of repression of EVI1, Mir-96, and even GLUT1 seem to abound in Pancreatic cancer.  What is of fascination is that GLUT 1 that we reported to be linked to HIF-1 and VHL and antioxidants, is said to be "downstream from c-MYC" the gene amplifier! (proliferative by excellence)  DPC4 must act on c-MYC through this conduit!   The VHL will impact EGFR and sure enough angiogenesis could be "depressed" impairing delivery (and effectiveness) of Chemotherapy in these disease.  Only Microtubule effect will come to concur this of course!(affecting the NOTCH!)
It is now evident that to slow down Pancreatic cancer
we should focus on
Disturbing ions channel, watch the FAK, impacting on Actin metabolism, expanding GLUT1, block c-MYC
and let's go to work!

ONE Thing THOUGH, the Devil Wnt is not far (when NOTCH is awaken)!

1.KRAS, " normal tissue signaling, and the mutation of a KRAS gene is an essential step in the development of many cancers.^[3] Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways. KRAS is usually tethered to cell membranes because of the presence of an isoprenyl group on its C-terminus." wikipedia
It is interesting to know that with KRAS activation follow the activation of RALGDS which through the Arrestins wake up the DVL (devil) preparing the cell to early proliferation and metastasis through the Wnt.
(wikipedia)