FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progressio...FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progression.We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues.In addition,the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma(n=75,P=0.0054)and lung adenocarcinoma(n=94,P=0.0330).Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6.Mechanistically,FRMD6 interacts and colocalizes with mTOR and S6K,which are the key molecules of the mTOR signaling pathway.FRMD6 markedly enhances the interaction between mTOR and S6K,subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells.Furthermore,knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^(−/−)gene KO MEFs and mice.Altogether,our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.展开更多
The exposure to plastic debris and associated pollutants for wildlife is of urgent concern,but little attention has been paid on the transfer of plastic additives from plastic debris to organisms.In the present study,...The exposure to plastic debris and associated pollutants for wildlife is of urgent concern,but little attention has been paid on the transfer of plastic additives from plastic debris to organisms.In the present study,the leaching of incorporated flame retardants (FRs),including polybrominated diphenyl ethers (PBDEs),alternative brominated FRs (AFRs),and phosphate flame retardants (PFRs),from different sizes of recycled acrylonitrile-butadiene-styrene (ABS) polymer were investigated in avian digestive fluids.The impact of co-ingested sediment on the leaching of additive-derived FRs in digestive fluids was also explored.In the recycled ABS,BDE 209 (715 μg/g) and 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE,1766 μg/g) had the highest concentrations among all target FRs.The leaching proportions of FRs were higher in finer sizes of ABS.The leaching proportions of FRs from recycled ABS increased with elevated logKow of FRs.In the tests with coexisted ABS and sediment,hexato deca-BDEs,BTBPE,and decabromodiphenyl ethane (DBDPE) migrated from ABS to sediment,which resulted in the less bioaccessible fractions of these FRs in gut fluids.More lipophilic chemicals tended to be adsorbed by sediment from ABS.The results suggest the migration of additive-derived FRs from plastics to other indigestible materials in digestive fluids.The findings in this study provide insights into the transfer of additive-derived FRs from plastics to birds,and indicate the significant contribution of FR-incorporated plastics to bioaccumulation of highly lipophilic FRs.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.82172972,81972609,81472734,31170711,81773199,81730071,81972616,81230051,and 81670626)the Beijing Natural Science Foundation(Nos.202084,7171005,7120002,and 7202080).
文摘FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progression.We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues.In addition,the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma(n=75,P=0.0054)and lung adenocarcinoma(n=94,P=0.0330).Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6.Mechanistically,FRMD6 interacts and colocalizes with mTOR and S6K,which are the key molecules of the mTOR signaling pathway.FRMD6 markedly enhances the interaction between mTOR and S6K,subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells.Furthermore,knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^(−/−)gene KO MEFs and mice.Altogether,our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.
基金supported by the National Natural Science Foundation of China(Nos.41603085 and 41877361)the Natural Science Foundation of Guangdong Province(No.2016A030310440)+2 种基金the Pearl River S&T Nova Program of Guangzhou(No.201806010185)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Z134)the Key Research Program of Frontier Sciences,the Chinese Academy of Science(No.QYZDJ-SSW-DQC018)
文摘The exposure to plastic debris and associated pollutants for wildlife is of urgent concern,but little attention has been paid on the transfer of plastic additives from plastic debris to organisms.In the present study,the leaching of incorporated flame retardants (FRs),including polybrominated diphenyl ethers (PBDEs),alternative brominated FRs (AFRs),and phosphate flame retardants (PFRs),from different sizes of recycled acrylonitrile-butadiene-styrene (ABS) polymer were investigated in avian digestive fluids.The impact of co-ingested sediment on the leaching of additive-derived FRs in digestive fluids was also explored.In the recycled ABS,BDE 209 (715 μg/g) and 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE,1766 μg/g) had the highest concentrations among all target FRs.The leaching proportions of FRs were higher in finer sizes of ABS.The leaching proportions of FRs from recycled ABS increased with elevated logKow of FRs.In the tests with coexisted ABS and sediment,hexato deca-BDEs,BTBPE,and decabromodiphenyl ethane (DBDPE) migrated from ABS to sediment,which resulted in the less bioaccessible fractions of these FRs in gut fluids.More lipophilic chemicals tended to be adsorbed by sediment from ABS.The results suggest the migration of additive-derived FRs from plastics to other indigestible materials in digestive fluids.The findings in this study provide insights into the transfer of additive-derived FRs from plastics to birds,and indicate the significant contribution of FR-incorporated plastics to bioaccumulation of highly lipophilic FRs.
基金supported by the National Natural Science Foundation of China(21703104,21673117 and 91956109)Nanjing Tech University(39837102)the SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials。
