CRITICAL POTENTIAL NOTIONS IN UNDERSTANDING TRIPLE NEGATIVE BREAST CANCERS

It all makes sense that Hypoxia induced by respiratory failure in a predominantly obese population will contribute to generation of Reactive Oxidative Species and that Over eating of sugar based products will worsen the events that will lead to HIF-1 gene excitation and probable amplification, which eventually involve the VHL (justifying the correlation of clear cell Renal cancer with obesity), and eventually amplify angiogenic genes (EGFR,VEGF).  This will end-up through Gerb2 connection gene, amplify the G proteins connected MAPK and could drive to a neoplastic process.  When p38-MAPK is involved there appears that the process will be accompanied by a significant cytokine release leading to an associated inflammatory process.  This is why anti-p38 is more looked into for its anti-inflammatory consequences rather than anti-neoplastic processes. For this inflammatory process to be successful, stimulation of the CREB must be suppressed, which it is in hypoxia. The level of Cyclic-AMP is also dampened as a result.

In the epigenic zone, amplification of the MAPK will ultimately amplify the MIFT (MIFT was first described under these conditions of amplified MAPK) with consequences that lead to dampening of Androgen activity if the MIFT interacts with PATZ1.

 If  MIFT interaction is mediated via PIAS3 binding^,, ER will be next to be knocked out


Wikipedia: "This interaction is mediated via PIAS3 binding to the STAT3 DNA binding domain. Hence, STAT3 transcriptional activity is inhibited by the physical prevention of its binding to target genes. Subsequently, PIAS3 was also found to be a regulator protein of other key transcription factors, including MITF,^[6] NFκB,^[7] SMAD ^[8] and estrogen receptor.^[9] PIAS3 protein also functions as a SUMO (small ubiquitin-like modifier)-E3 ligase"

Pretty soon, you have yourself a triple negative breast cancer!!!
(leading to the question is IL6 elevated in this disease?

MIFT involvement with TFE3 will engage HMGA-2 and prop the metastatic propensity in this disease (triple negative breast cancer).

The involvement of MIFT is obligatory since it will unlock the chromatin to allow access to nuclear material by chromatin modulation

TO BE CONTINUED