|
|
|
|
FGF2/FGFR1 regulates autophagy in FGFR1-amplified non-small cell lung cancer cells
|
|
|
|
|
|
|
|
نویسنده
|
yuan h. ,li z.-m. ,shao j. ,ji w.-x. ,xia w. ,lu s.
|
|
منبع
|
journal of experimental and clinical cancer research - 2017 - دوره : 36 - شماره : 1
|
|
چکیده
|
Background: autophagy is a conserved catabolic process to degrade cellular organelles. the role of autophagy in cancer development is complex. amplification of fibroblast growth factor receptor 1 (fgfr1) is one of the most frequent targets in lung squamous cell carcinoma (sqcc). whether fibroblast growth factor 2 (fgf2)/fgfr1 contributes to the regulation of autophagy remains elusive. methods: autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (lc3),formation of gfp-lc3 puncta,and monodansylcadaverine (mdc) staining. the effect of autophagy inhibition on cell survival was assessed by cell viability and apoptosis assays. results: we elucidated that fgfr1 activation suppressed autophagy. pharmacological or genetic inhibition of fgfr1 by azd4547 or fgfr1 short hairpin rna (shrna) induced autophagy in fgfr1-amplified non-small cell lung cancer (nsclc) cells,h1581 and h520 cells. mechanistic study revealed that the induction of autophagy by fgfr1 inhibition was mediated through inhibiting the erk/mapk pathway not by akt pathway,accompanied by upregulation of beclin-1. furthermore,activation of erk/mapk by transfection with a constitutively active mek1 (camek1) construct or knockdown of beclin-1 by rnai could attenuate autophagy induced by fgfr1 inhibition. beclin-1 expression was inversely correlated with mek1 phosphorylation. inhibition of autophagy by beclin-1 silencing could enhance apoptosis after azd4547 treatment in h1581 and h520 cells. high levels of lc3b mrna was a marker of poor prognosis in nsclc patients. conclusions: simultaneously inhibiting fgfr1 and autophagy could enhance cell death which should be further explored in vivo. © 2017 the author(s).
|
|
کلیدواژه
|
Autophagy; Beclin-1; ERK; FGFR1; NSCLC
|
|
آدرس
|
shanghai lung cancer center,shanghai chest hospital,shanghai jiao tong university,shanghai,200030,china,school of biomedical engineering,med-x research institute,shanghai jiao tong university,shanghai,200030, China, shanghai lung cancer center,shanghai chest hospital,shanghai jiao tong university,shanghai,200030, China, school of biomedical engineering,med-x research institute,shanghai jiao tong university,shanghai,200030, China, shanghai lung cancer center,shanghai chest hospital,shanghai jiao tong university,shanghai,200030,china,school of biomedical engineering,med-x research institute,shanghai jiao tong university,shanghai,200030, China, school of biomedical engineering,med-x research institute,shanghai jiao tong university,shanghai,200030, China, shanghai lung cancer center,shanghai chest hospital,shanghai jiao tong university,shanghai,200030, China
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|