The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappoin...The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappointing due to crosstalk with other signals.Here,we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma(HCC)cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)activity.In response to ligand binding,IGF-1Rβis translocated into the ER byβ-arrestin2(β-arr2).Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ.SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβlevels.ER IGF-1Rβphosphorylates SERCA2 on Tyr^(990)to enhance its activity.Mutation of SERCA2-Tyr^(990)disrupted the interaction of ER IGF-1Rβwith SERCA2,and therefore ER IGF-1Rβfailed to promote SERCA2 activity.The enhancement of SERCA2 activity triggered Ca_(ER)^(2+)perturbation,leading to an increase in autophagy.Thapsigargin blocked the interaction between SERCA2and ER IGF-1Rβand therefore SERCA2 activity,resulting in inhibition of HCC growth.In conclusion,the translocation of IGF-1R into the ER triggers Ca_(ER)^(2+)perturbation by enhancing SERCA2 activity through phosphorylating Tyr^(990)in HCC.展开更多
Hydrothermal treatment of calcium oxide and boric acid mixtures at temperaturesbetween 234 ℃ and 300 ℃ has produced a colorless, transparent, orthorhombic compound Ca2B6O11 · H2O. Of the seven known members of ...Hydrothermal treatment of calcium oxide and boric acid mixtures at temperaturesbetween 234 ℃ and 300 ℃ has produced a colorless, transparent, orthorhombic compound Ca2B6O11 · H2O. Of the seven known members of the series of hydrated dicalcium hexaborate containing boron-oxygen six-membered ring anionic group (B3O8)7, only the title compound has been found to have the nonlinear optical effect. The second harmanic generation (SHG) effect of its crystal is larger than that of KH2PO4 (KDP). The reflection spectrum has shown that this compound has no absorption in the experimental wavelength range (800-240 nm). Its crystal structure is favorable for generating the nonlinear optical effect.展开更多
基金supported by the National Natural Science Foundation of China(81973350,China)supported by the National Natural Science Foundation of China(81872884 and 82173841,China)Beijing Natural Science Foundation(7222253,China)。
文摘The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappointing due to crosstalk with other signals.Here,we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma(HCC)cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)activity.In response to ligand binding,IGF-1Rβis translocated into the ER byβ-arrestin2(β-arr2).Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ.SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβlevels.ER IGF-1Rβphosphorylates SERCA2 on Tyr^(990)to enhance its activity.Mutation of SERCA2-Tyr^(990)disrupted the interaction of ER IGF-1Rβwith SERCA2,and therefore ER IGF-1Rβfailed to promote SERCA2 activity.The enhancement of SERCA2 activity triggered Ca_(ER)^(2+)perturbation,leading to an increase in autophagy.Thapsigargin blocked the interaction between SERCA2and ER IGF-1Rβand therefore SERCA2 activity,resulting in inhibition of HCC growth.In conclusion,the translocation of IGF-1R into the ER triggers Ca_(ER)^(2+)perturbation by enhancing SERCA2 activity through phosphorylating Tyr^(990)in HCC.
文摘Hydrothermal treatment of calcium oxide and boric acid mixtures at temperaturesbetween 234 ℃ and 300 ℃ has produced a colorless, transparent, orthorhombic compound Ca2B6O11 · H2O. Of the seven known members of the series of hydrated dicalcium hexaborate containing boron-oxygen six-membered ring anionic group (B3O8)7, only the title compound has been found to have the nonlinear optical effect. The second harmanic generation (SHG) effect of its crystal is larger than that of KH2PO4 (KDP). The reflection spectrum has shown that this compound has no absorption in the experimental wavelength range (800-240 nm). Its crystal structure is favorable for generating the nonlinear optical effect.
