Matches in SemOpenAlex for { <https://semopenalex.org/work/W3204643005> ?p ?o ?g. }
- W3204643005 abstract "ABSTRACT Cancers represent complex autonomous systems, displaying self-sufficiency in growth signaling. Autonomous growth is fueled by a cancer cell’s ability to ‘secrete-and-sense’ growth factors: a poorly understood phenomenon. Using an integrated systems and experimental approach, here we dissect the impact of a feedback-coupled GTPase circuit within the secretory pathway that imparts secretion-coupled autonomy. The circuit is assembled when the Ras-superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαβγ and their corresponding GAPs and GEFs are coupled by GIV/Girdin, a protein that is known to fuel aggressive traits in diverse cancers. One forward and two key negative feedback loops within the circuit create closed-loop control (CLC), allow the two GTPases to coregulate each other, and convert the expected switch-like behavior of Arf1-dependent secretion into an unexpected dose response alignment behavior of sensing and secretion. Such behavior translates into cell survival that is self-sustained by stimulus-proportionate secretion. Proteomic studies and protein-protein interaction network analyses pinpoint growth factors (e.g., the epidermal growth factor; EGF) as a key stimuli for such self-sustenance. Findings highlight how enhanced coupling of two biological switches in cancer cells is critical for multiscale feedback control to achieve secretion-coupled autonomy of growth factors. SYNOPSIS IMAGE STANDFIRST TEXT This work defines the inner workings of a Golgi-localized molecular circuitry comprised of coupled GTPases, which empowers cells to achieve self-sufficiency in growth factor signaling by creating a secrete-and-sense autocrine loop. HIGHLIGHTS/MAIN FINDINGS Modeling and experimental approaches were used to dissect a coupled GTPase circuit. Coupling enables closed loop feedback and mutual control of GTPases. Coupling generates dose response alignment behavior of sensing and secretion of growth factors. Coupling is critical for multiscale feedback control to achieve secretion-coupled autonomy." @default.
- W3204643005 created "2021-10-11" @default.
- W3204643005 creator A5005498435 @default.
- W3204643005 creator A5009748898 @default.
- W3204643005 creator A5013498569 @default.
- W3204643005 creator A5035734477 @default.
- W3204643005 creator A5038389980 @default.
- W3204643005 creator A5059670809 @default.
- W3204643005 creator A5061598575 @default.
- W3204643005 creator A5063009651 @default.
- W3204643005 creator A5071425686 @default.
- W3204643005 creator A5075435485 @default.
- W3204643005 creator A5085015270 @default.
- W3204643005 creator A5086150502 @default.
- W3204643005 date "2021-03-19" @default.
- W3204643005 modified "2023-10-10" @default.
- W3204643005 title "A Circuit for Secretion-coupled Cellular Autonomy in Multicellular Eukaryotes" @default.
- W3204643005 cites W125396517 @default.
- W3204643005 cites W1499112972 @default.
- W3204643005 cites W1509686758 @default.
- W3204643005 cites W1516922966 @default.
- W3204643005 cites W1548266878 @default.
- W3204643005 cites W1551952768 @default.
- W3204643005 cites W1572656384 @default.
- W3204643005 cites W1590222219 @default.
- W3204643005 cites W1910609371 @default.
- W3204643005 cites W1955181723 @default.
- W3204643005 cites W1964252660 @default.
- W3204643005 cites W1964619469 @default.
- W3204643005 cites W1964702288 @default.
- W3204643005 cites W1966990402 @default.
- W3204643005 cites W1967573809 @default.
- W3204643005 cites W1972189437 @default.
- W3204643005 cites W1973383183 @default.
- W3204643005 cites W1976731691 @default.
- W3204643005 cites W1988836230 @default.
- W3204643005 cites W1989594281 @default.
- W3204643005 cites W2002984398 @default.
- W3204643005 cites W2006943139 @default.
- W3204643005 cites W2007391357 @default.
- W3204643005 cites W2010984379 @default.
- W3204643005 cites W2011428375 @default.
- W3204643005 cites W2012034410 @default.
- W3204643005 cites W2014202134 @default.
- W3204643005 cites W2014333610 @default.
- W3204643005 cites W2014794373 @default.
- W3204643005 cites W2015594324 @default.
- W3204643005 cites W2017451004 @default.
- W3204643005 cites W2024256271 @default.
- W3204643005 cites W2027764322 @default.
- W3204643005 cites W2028420847 @default.
- W3204643005 cites W2033509933 @default.
- W3204643005 cites W2034269086 @default.
- W3204643005 cites W2035807916 @default.
- W3204643005 cites W2040278595 @default.
- W3204643005 cites W2053538636 @default.
- W3204643005 cites W2064820900 @default.
- W3204643005 cites W2071896628 @default.
- W3204643005 cites W2072817575 @default.
- W3204643005 cites W2073968654 @default.
- W3204643005 cites W2075889896 @default.
- W3204643005 cites W2086434567 @default.
- W3204643005 cites W2089333852 @default.
- W3204643005 cites W2094614586 @default.
- W3204643005 cites W2100640599 @default.
- W3204643005 cites W2104063456 @default.
- W3204643005 cites W2105924489 @default.
- W3204643005 cites W2108341352 @default.
- W3204643005 cites W2109280287 @default.
- W3204643005 cites W2110699703 @default.
- W3204643005 cites W2112933240 @default.
- W3204643005 cites W2116641466 @default.
- W3204643005 cites W2119963394 @default.
- W3204643005 cites W2120988439 @default.
- W3204643005 cites W2121491527 @default.
- W3204643005 cites W2123558100 @default.
- W3204643005 cites W2124357987 @default.
- W3204643005 cites W2127248728 @default.
- W3204643005 cites W2137247515 @default.
- W3204643005 cites W2148252058 @default.
- W3204643005 cites W2153624566 @default.
- W3204643005 cites W2158422128 @default.
- W3204643005 cites W2160698849 @default.
- W3204643005 cites W2169589032 @default.
- W3204643005 cites W2169961781 @default.
- W3204643005 cites W2175665218 @default.
- W3204643005 cites W2195727561 @default.
- W3204643005 cites W2222365833 @default.
- W3204643005 cites W2225194633 @default.
- W3204643005 cites W2253580930 @default.
- W3204643005 cites W2274282959 @default.
- W3204643005 cites W2285982465 @default.
- W3204643005 cites W2289292317 @default.
- W3204643005 cites W2292197956 @default.
- W3204643005 cites W2332208114 @default.
- W3204643005 cites W2336702483 @default.
- W3204643005 cites W2509255951 @default.
- W3204643005 cites W2520441132 @default.
- W3204643005 cites W2542418519 @default.
- W3204643005 cites W2566638417 @default.