Monday, September 9, 2013

NOTCH NOTCH, who's there!?

NOTCH NOTCH NOTCH every single where!

Research at NIH reported that metastasis occur when the cancer cell has created an invasive extension called INVADOPODIA.  To form these invadopodia the cell has to modify its membranous boundaries.
Cancer cells live in a relatively hypoxic milieu which activates HIF-1 the Hypoxia Induced Factor, which of course will go on to induce formation of transcription factors to deal with the hypoxic milieu.  But one of the target  pathways turned on by HIF1 is "THE NOTCH SIGNALING PATHWAY, which an important means of cell to cell communication" (Begona Diaz et al.).   And you just know that the NOTCH is going to do its things in the epigenetic area which include activating c-MYC, inducing  Cytokine formation, inducing growth factors including those involving epidermal growth factor.  Indeed at appropriate Integrins, the NOTCH resulting effect is to FLIP-IN HB-EGF (heparin-binding Epidermal Growth Factor) and FLOP-OUT Metallopreotease.  One of the Integrins involved is ADAMS-12 which is further involved under the metalloproteases effect, amplifying extracellular events and on the membrane, prompting the INVADOPODIA.   According to these authors "ADAMS-12 is an important effector of INVADOPODIA" and ensures the Cross talk NOTCH versus EGFR.  And with the cross talk EGFR versus VEGF. path to Metastatasis enabling is crossed!

The NOTCH, so omnipresent, it is sometimes ignored by distracted scientists! 

HOW MANY TARGETS are listed here!?
ADAM12, an effector of invadopodia signaling
ADAM12 functions in the cell by cutting other proteins. Hypoxia and notch signaling increased the amount of ADAM12 in the cell. Media obtained from hypoxic cells but not cells that lacked ADAM12-induced invadopodia formation in cells growing under normal oxygen levels. Diaz concluded that ADAM12 activity released an invadopodia-promoting factor. One of the potential candidates was heparin-binding epidermal growth factor (HB-EGF).
Crosstalk between notch and EGFR signaling linked by ADAM12
HB-EGF, which can be released from the cell by ADAM12’s activity, activates the epidermal growth factor receptor (EGFR). Adding HB-EGF to normoxic cells promoted invadopodia formation, while inhibiting HB-EGF decreased invadopodia in hypoxic cells. Inhibiting any component of the upstream pathway, Notch or ADAM12, prevented cells from releasing HB-EGF in response to hypoxia.
- See more at: http://beaker.sanfordburnham.org/2013/08/kicking-invasion-up-a-notch/#sthash.xhKP53nR.dpuf
ADAM12, an effector of invadopodia signaling
ADAM12 functions in the cell by cutting other proteins. Hypoxia and notch signaling increased the amount of ADAM12 in the cell. Media obtained from hypoxic cells but not cells that lacked ADAM12-induced invadopodia formation in cells growing under normal oxygen levels. Diaz concluded that ADAM12 activity released an invadopodia-promoting factor. One of the potential candidates was heparin-binding epidermal growth factor (HB-EGF).
Crosstalk between notch and EGFR signaling linked by ADAM12
HB-EGF, which can be released from the cell by ADAM12’s activity, activates the epidermal growth factor receptor (EGFR). Adding HB-EGF to normoxic cells promoted invadopodia formation, while inhibiting HB-EGF decreased invadopodia in hypoxic cells. Inhibiting any component of the upstream pathway, Notch or ADAM12, prevented cells from releasing HB-EGF in response to hypoxia.
- See more at: http://beaker.sanfordburnham.org/2013/08/kicking-invasion-up-a-notch/#sthash.xhKP53nR.dpuf
ADAM12, an effector of invadopodia signaling
ADAM12 functions in the cell by cutting other proteins. Hypoxia and notch signaling increased the amount of ADAM12 in the cell. Media obtained from hypoxic cells but not cells that lacked ADAM12-induced invadopodia formation in cells growing under normal oxygen levels. Diaz concluded that ADAM12 activity released an invadopodia-promoting factor. One of the potential candidates was heparin-binding epidermal growth factor (HB-EGF).
Crosstalk between notch and EGFR signaling linked by ADAM12
HB-EGF, which can be released from the cell by ADAM12’s activity, activates the epidermal growth factor receptor (EGFR). Adding HB-EGF to normoxic cells promoted invadopodia formation, while inhibiting HB-EGF decreased invadopodia in hypoxic cells. Inhibiting any component of the upstream pathway, Notch or ADAM12, prevented cells from releasing HB-EGF in response to hypoxia.
- See more at: http://beaker.sanfordburnham.org/2013/08/kicking-invasion-up-a-notch/#sthash.xhKP53nR.dpuf

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