BACKGROUND Anoctamin 5(ANO5)/transmembrane protein 16E belongs to the ANO/transmembrane protein 16 anion channel family.ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid sc...BACKGROUND Anoctamin 5(ANO5)/transmembrane protein 16E belongs to the ANO/transmembrane protein 16 anion channel family.ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types.Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types.However,it remains unclear whether ANO5 acts as a plasma membrane chloride channel,and its expression and functions in gastric cancer(GC)have not been investigated.AIM To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.METHODS Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines,and changes in cell proliferation,cell cycle progression,apoptosis,and cellular movement were assessed.The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis.Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.RESULTS Reverse transcription-quantitative polymerase chain reaction(PCR)and western blotting demonstrated high ANO5 mRNA and protein expression,respectively,in NUGC4 and MKN45 cells.In these cells,ANO5 silencing inhibited cell proliferation and induced apoptosis.In addition,the knockdown of ANO5 inhibited G1-S phase progression,invasion,and migration.The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes,such as CDKN1A,CDK2/4/6,CCNE2,and E2F1,in ANO5-depleted NUGC4 cells.The expression of these genes was verified using reverse transcription-quantitative PCR.Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis.Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC(P=0展开更多
The development of uterine cervical cancer is primarily attributed to infection by high-risk human papillomaviruses(HR-HPVs).E5,E6 and E7,the three early oncoproteins of HR-HPVs,have been implicated in initiation and ...The development of uterine cervical cancer is primarily attributed to infection by high-risk human papillomaviruses(HR-HPVs).E5,E6 and E7,the three early oncoproteins of HR-HPVs,have been implicated in initiation and progression of cervical cancer.The intricate molecular mechanisms that orchestrate aberrant cellular transformations to establish carcinoma of the cervical epithelium following viral infections are poorly understood.Here,we discuss how deregulation of three major cell fate regulatory pathways,Hedgehog,Wnt and Notch,and cell survival strategies involving EGFR signaling and G1/S checkpoint contribute towards cervical cancer development and progression.Further exploration of protein interaction database has revealed several genes that are involved in cervical cancer initiation and progression,and the two crucial"driver"genes,MYC and CTNNB1(β-catenin),have been identified as major players in protein-protein interaction network.GSK3βemerged as the key mediator of crosstalk between Hedgehog,Wnt and Notch signaling pathways.GSK3βregulates cytoplasmic stabilization and nuclear translocation ofβ-catenin,which further impacts the expression of MYC,critical for cell cycle progression.Collectively,our analyses suggest that combinatorial therapeutic targeting of these proteins may be more effective in blocking cervical cancer initiation and progression.展开更多
基金Supported by Japan Society for the Promotion of Science,No.21K08689,No.21K16456,No.20K09016,No.20K09084,No.19K09202 and No.19K09182.
文摘BACKGROUND Anoctamin 5(ANO5)/transmembrane protein 16E belongs to the ANO/transmembrane protein 16 anion channel family.ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types.Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types.However,it remains unclear whether ANO5 acts as a plasma membrane chloride channel,and its expression and functions in gastric cancer(GC)have not been investigated.AIM To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.METHODS Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines,and changes in cell proliferation,cell cycle progression,apoptosis,and cellular movement were assessed.The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis.Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.RESULTS Reverse transcription-quantitative polymerase chain reaction(PCR)and western blotting demonstrated high ANO5 mRNA and protein expression,respectively,in NUGC4 and MKN45 cells.In these cells,ANO5 silencing inhibited cell proliferation and induced apoptosis.In addition,the knockdown of ANO5 inhibited G1-S phase progression,invasion,and migration.The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes,such as CDKN1A,CDK2/4/6,CCNE2,and E2F1,in ANO5-depleted NUGC4 cells.The expression of these genes was verified using reverse transcription-quantitative PCR.Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis.Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC(P=0
文摘The development of uterine cervical cancer is primarily attributed to infection by high-risk human papillomaviruses(HR-HPVs).E5,E6 and E7,the three early oncoproteins of HR-HPVs,have been implicated in initiation and progression of cervical cancer.The intricate molecular mechanisms that orchestrate aberrant cellular transformations to establish carcinoma of the cervical epithelium following viral infections are poorly understood.Here,we discuss how deregulation of three major cell fate regulatory pathways,Hedgehog,Wnt and Notch,and cell survival strategies involving EGFR signaling and G1/S checkpoint contribute towards cervical cancer development and progression.Further exploration of protein interaction database has revealed several genes that are involved in cervical cancer initiation and progression,and the two crucial"driver"genes,MYC and CTNNB1(β-catenin),have been identified as major players in protein-protein interaction network.GSK3βemerged as the key mediator of crosstalk between Hedgehog,Wnt and Notch signaling pathways.GSK3βregulates cytoplasmic stabilization and nuclear translocation ofβ-catenin,which further impacts the expression of MYC,critical for cell cycle progression.Collectively,our analyses suggest that combinatorial therapeutic targeting of these proteins may be more effective in blocking cervical cancer initiation and progression.
