Showing posts with label fibroblasts. Show all posts
Showing posts with label fibroblasts. Show all posts

Friday, April 5, 2013

STRATIFIN (IN OVARIAN CANCER)

LAM et al.

 " Stratifin, also known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1 expression in dermal fibroblasts.  Treatment of dermal fibroblasts with stratifin resulted in rapid and transient upregulation of c-jun and c-fos mRNA levels.  Stratifin was demonstrated to increase MMP-1 protein levels. Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis. Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion. In conclusion, stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and MAPK pathway."

Our interpretation is that stratifin is part of an intergrin, its release in the Cytoplasm indeed stimulate MAPK C-JUN and c-fos.  This means it is interpretated by the cell as a chemical stressor. The NF-kB is not far away.  One of the most important hidden information here is the note by the authors that there is an increase of ELK4/Sap1.

ELK4 has been shown to interact with Serum response factor[4][5] and BRCA1.[6]

Serum response factor has been shown to interact with NFYA,[10] Src,[11] CREB-binding protein,[12] GTF2I,[13][14] ATF6,[15] Nuclear receptor co-repressor 2,[16] CEBPB,[17][18] GATA4,[19][20] Myogenin,[21][22] GTF2F1,[23][24] TEAD1,[25] ELK4,[15][26] Promyelocytic leukemia protein[12] and ASCC3.[27]
(wikipedia)

(PLEASE, WHEN A MOLECULE INTERACT WITH THIS MANY MOLECULE, IT IS A PERFECT, LEGITIMATE TARGET FOR THERAPY, AND SFR DOES)

ELK4 therefore control BRCA1 and serum response factor which control NFYA.  This uncover what the cancer cell has to do to start the neoplastic process.  It has to derail genetic repair by abrogating the action of BRAC1, but it also has to take controles of CBF complexes  and NFYA and ZHXY.  Remember CBF complexes control the direction of the metabolism, In essence, when it comes to function in the cell,  the role of Core Binding Factors (CBF) is indistinguishable from that of TRANSCRIPTION FACTORS.  They all impose the direction that the cell metabolism should take.

Remember also that because the Stratifin engages the MAPK mostly through the certain well selected CDK, it will tend to stop cell division.  In Breast cancer, Stratifin is one of the earliest methylated gene slated for silencing.

CDO1:
 Cysteine dioxygenase type I, IS A GENE CONTROLLING  CYSTEIN METABOLISM. DEEP ANALYSIS BRINGS THIS GENE TO ELECTRON EXCHANGE FOR THE FORMATION OF CYTOCHROME C, THE WAY TO APOPTOSIS.  THE CANCER CELL QUICKLY METHYLATES THIS GENE EARLY AND MUTATION HAS BEEN LINKED TO PROGNOSIS
 (WORK FROM CORNELL UNIVERSITY)