* Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells.
- Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis and marked lethality. Rho monomeric G protein levels are increased in pancreatic cancer tissue. As the mechanisms underlying PDAC malignancy are little understood, we investigated the role for cAMP in regulating monomeric G protein regulated invasion and migration of pancreatic cancer cells. Treatment of PDAC cells with cAMP elevating agents that activate adenylyl cyclases, forskolin, protein kinase A (PKA), 6-Bnz-cAMP, or the cyclic nucleotide phosphodiesterase inhibitor cilostamide significantly decreased migration and Matrigel invasion of PDAC cell lines. Inhibition was dose-dependent and not significantly different between forskolin or cilostamide treatment. cAMP elevating drugs not only blocked basal migration, but similarly abrogated transforming-growth factor-β-directed PDAC cell migration and invasion. The inhibitory effects of cAMP were prevented by the pharmacological blockade of PKA. Drugs that increase cellular cAMP levels decreased levels of active RhoA or RhoC, with a concomitant increase in phosphorylated RhoA. Diminished Rho signaling was correlated with the appearance of thickened cortical actin bands along the perimeter of non-motile forskolin or cilostamide-treated cells. Decreased migration did not reflect alterations in cell growth or programmed cell death. Collectively these data support the notion that increased levels of cAMP specifically hinder PDAC cell motility through F-actin remodeling.
Overview of noun level
The noun level has 8 senses (first 6 from tagged texts)
1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a
moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree")
2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of
the highest grade")
3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or
especially in a process; "a remarkable degree of frankness"; "at what stage are the social
sciences?")
4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the
same level")
5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered
in a tube of liquid)
6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car
on the level")
7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor
communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions
on many strata simultaneously")
8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single
position along a vertical scale; "what level is the office on?")
Overview of verb level
The verb level has 6 senses (first 3 from tagged texts)
1. (4) level -- (aim at; "level criticism or charges at somebody")
2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make
flat with the ground; "The building was levelled")
3. (1) flush, level, even out, even -- (make level or straight; "level the ground")
4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at
me")
5. level -- (talk frankly with; lay it on the line; "I have to level with you")
6. level, level off -- (become level or even; "The ground levelled off")
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