Data from: Cavin-3 dictates the balance between ERK and Akt signaling

Cavin-3 is a tumor suppressor protein of unknown function. Using a combination of in vivo knockout and in vitro gain/loss of function approaches, we show that cavin-3 dictates the balance between ERK and Akt signaling. Loss of cavin-3 increases Akt signaling at the expense of ERK, while gain of cavin-3 increases ERK signaling at the expense Akt. Cavin-3 facilitates signal transduction to ERK by anchoring caveolae, a lipid-raft specialization that contains an ERK activation module, to the membrane skeleton of the plasma membrane. Loss of cavin-3 reduces the number of caveolae, thereby separating this ERK activation module from signaling receptors. Loss of cavin-3 promotes Akt signaling through suppression of EGR1 and PTEN. The in vitro consequences of the loss of cavin-3 include induction of Warburg metabolism (aerobic glycolysis), accelerated cell proliferation and resistance to apoptosis. The in vivo consequences of cavin-3 loss are increased lactate production and cachexia.Cavin-3是一种功能未知的肿瘤抑制蛋白。本研究联合体内基因敲除（in vivo knockout）与体外功能获得/功能缺失实验策略，证实Cavin-3可调控ERK与Akt信号通路间的平衡。Cavin-3缺失会以ERK信号通路为代价增强Akt信号通路，而过表达Cavin-3则会以Akt信号通路为代价增强ERK信号通路。Cavin-3通过将携带ERK激活模块的脂筏特化结构——微囊泡（caveolae）锚定至细胞质膜的膜骨架，促进ERK信号转导。Cavin-3缺失会减少微囊泡的数量，进而使该ERK激活模块与信号受体发生分离。Cavin-3缺失可通过抑制EGR1与PTEN来促进Akt信号通路的激活。体外实验中，Cavin-3缺失会诱导瓦伯格代谢（Warburg metabolism，即有氧糖酵解）、加速细胞增殖并产生细胞凋亡抵抗。体内实验中，Cavin-3缺失会导致乳酸生成增多与恶病质（cachexia）的发生。