TMEM206 Promotes The Malignancy Of Colorectal Cancer Cells By Interacting With AKT And Extracellular Signal-regulated Kinase Signalling Pathways

Background The roles of TMEM206,a new transmembrane protein,in cancer,including colorectal cancer(CRC),are unknown.Related family members,including TMEM16 A,TMEM132A,and TMEM176 B,have been shown to be involved in various biological behaviours.Additionally,TMEM88 had been reported to promote non-small cell lung cancer.In this study,we examined the roles of TMEM206 in CRC.Methods Real-time reverse transcription polymerase chain reaction was used to measure TMEM206 mRNA levels in clinical and transfected cell lines.Western blotting was used to detect the expression of TMEM206 in clinical specimens and transfected cell lines.Immunohistochemistry was used to determine the relationship between TMEM206 expression levels and clinical data.TMEM206 was up-regulated and silenced using plasmid and small interfering RNA,respectively.Protein expression levels and signaling pathway regulation were verified by Western blot analysis.The potential role of TMEM206 in CRC was tested using colony formation,MTT,cell migration and invasion assays,and flow cytometry analysis.Co-immunoprecipitation was used to evaluate the interaction between TMEM206 and AKT,and co-immunoprecipitation was used to detect the tight junction between TMEM206 protein and ERK protein.Results To study the clinical significance of TMEM206 expression in CRC tissues,the results showed that TMEM206 mRNA and protein levels in CRC tissues were higher thanthose in paired normal adjacent tissues(p < 0.05).TMEM206 overexpression was positively correlated with cancer T and UICC(p < 0.05)and negatively correlated with CRC differentiation(p = 0.015).Up-regulation or silencing of TMEM206 promotes or inhibits the proliferation of CRC cells and positively or negatively regulates the levels of phospho-AKT and downstream signaling pathway components(phospho-glycogen synthase kinase 3? and cyclin D1,respectively).Furthermore,silencing of TMEM206 in cell lines arrests CRC cells in the G1 phase of the cell cycle.In addition,upregulation or silencing of TMEM206 increased or decreased cell invasion and migration,respectively,and positively or negatively altered levels of phospho-extracellular signal-regulated kinase(ERK)and phosphorylated focal adhesion kinase 397,respectively.Co-immunoprecipitation demonstrated AKT and TMEM206 protein interactions,and then we confirmed that there is no close relationship between TMEM206 and ERK proteins.We also initially found that there is a bridge protein between the AKT pathway and the ERK pathway,which together play a role in affecting the CRC nausea phenotype.In addition,TMEM206 promotes the development and progression of CRC by enhancing the interaction between AKT and ERK signaling pathways.Conclusion TMEM206 controlled the progression of CRC by accelerating CRC cell proliferation and promoting CRC cell migration and invasion.The target of TMEM206 may be AKT,which is known to be involved in modulating the biological behaviours of various cancers.