ADAPTER GENES

Nothing is simple but yet as determinant as an Adapter gene.
The cell continues to amaze scientists.
When a stimulant attaches to a receptor, the 2, stimulant and receptor, enter the cell in some cases, detaching from the membrane and enter the cell.  Most of the time there is a triggering of main pathways such as the RAS, but sometimes, at the site of attachment, the raw edges of the membrane are not healing and wage their own war...here it is the focal Adhesion kinases that are going to war.  Now, that war is not necessarily random.  Depending on the nature of the stimulant and receptor involved, the FAK can turn to a Gerb2, Lyn or Flyn with a totally new orientation in the metabolism of the cell.  Sometimes the adapter is simply a b-cell linker or it is a T-cell linker and the cell will follow that path or attract these different cells.  It may use RUS1 to block the excited RAS that we spoke about or orient the cell to Rho in order to exacerbate metastasis.  
These linkers are a way to control differentiation, but when erratic, they could compromise the host!  Certain genes are destined to help many proteins such as a portion of an Antibody, imagine them wrongly linked to some other gene leading to unwarranted  multiplication! Things are set for hematologic malignancies!

Preliminary impression:
- Attachment to Lyn- B cell differentiation (some) and if Gerb2 involved, T cell differentiation definitely if the stimulant is TGF alpha!
Flyn- well may be muscle dystrophy, of some form.
Attachment to TBS - mental retardation
Lck-depression such as seen with chronic autoimmune disease (locus Coereleus)

Watch your Adaptor genes carefully!  Otherwise things are going in a direction you may not wish!

Profiling through at the CRBCM!

At the CRBCM something is coming through:

1. Deterioration at membrane receptor by lack of stimulation or "false or abnormal stimulation" could not only alter the nature of the "glycan" covering the protein portion of the receptor, but also induce stress like molecules.(HSP)
2. As a result of receptor failure new cytokines and TGFs are secreted which unfortunately fail at the initial receptor, but induce other receptors, amplifying standard pathways like RAS or PIK
3. Certains TGFs have an intrinsic power to maintain life of cells no matter what and induce metastasis.
4. Certain genes have an auto-phosphorylation or self-limiting mechanism that can easily go wrong  (RAS, FAK) driving to neoplastic process
5. FAK plays a larger role in aggressive prostate cancer than it has been recognized!
6. FAK has a closer relation to Androgen than recognized
7. NOTCH has closer relation with MEK and "stem cell potential" than recognized.
8. FAK disturbance prominence in cancer explains its sensitivity to Taxanes!  That is on top of Microtubule disturbances induced by the drug!
9. Metalloproteases are the ultimate Biomarkers of membrane events !
10.  Epigenetic methylation and its patterns are one of the largest mystery still to be elucidated!

Nomenclature of 2 important genes in Ovarian cancer !

1.RASSF1A:  One of the thing cancer cell do is to Methylate some genes in order to block its path to death.
it appears this gene is a critical door to shut or disable.  It not only decrease the significance of RAS and MAPK in the pathogenesis of tumor that harbor this mutation.   It also remove blockage to proliferation by desensitizing the cell to the effect of P53, Cyclins.  Desensitize the cell to Death Receptor 6 and its Fas connection.  RASSF1a, demethylation is a valid target in ovarian cancer.

2.HNF1B:  " Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of HNF1A have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA."
 (Laura Pelletier et al)
This gene is the gene of differentiation for liver formation, it has the structure of a CBF (core binding Factor) therefore has a subunit binding the DNA, therefore silencing that portion, and another subunit having locations for enzymatic proteins or molecular structures that directly assume various functions intended by the cell (formation of Albumin, alpha Antitrypsine, and Beta Fibrinogen).
Interestingly enough, Steatosis is a prominent feature here.  This structure and gene may be of interest in LIPOSARCOMA?  
DOES ACTIVATION OF MTOR DEMONSTRATED HERE OPEN THE DOOR TO THE USE OF MTOR IN LIPOSARCOMA?

INTERESTING DEBATES

1.NF1 Mutation is upstream from
BRAF
and MTOR
But NF-1 is Mutated in Melanoma
can infusion of protein resulting from NF-1 be used to strengthen effect of MTOR inhibitor and BRAF inhibitor by maintaining these pathways open!

2.  Discriminating Redundancy in cellular language
same gene base corresponding to same Amino Acid
same receptors at membrane being sensitive by different stimuli
but when it comes to the RAS, nature and intensity need to matter and this also a function of tissue involved!
some time however the nature of the stimulus is more important particularly inside the cell where ie HP90 seems to stimulate more the CoN to achieve PTEN suppression. And you know that CoM stimulation raise Bcl2 level...we will say more in our upcoming article of langaue of the cell as it pertains to pathways!

3. PTEN is repressed by low expression of gene or mislocalization (reported PNUTS 'role) at Nuclear level or both?