The Role Of PTBP1 In Invasion And Metastasis Of Breas Cancer Cells

Breast cancer is the most common malignant disease in women worldwide.Noticeably,breast cancer metastasis is primarily responsible for the mortality from solid tumors.The distant metastasis of breast cancer is an extremely complicated process,which involves the infiltration of primary cancer cells into blood circulation,and formation of metastatic colonization in new tumor microenvironment.Making further research on the metastasis of breast cancer will provide theory basis for detection and treatment.Changes in cell phenotype between epithelial and mesenchymal states,defined as epithelial–mesenchymal transition(EMT).EMT is a complex molecular and cellular programme,which epithelial cells shed their differentiated characteristics,and acquire instead mesenchymal features,including motility,invasiveness.Accumulating evidence suggests a critical role in cancer progression.Kinds of transcription factors have been found involved in EMT progression,such as Snail?Twist?ZEB.Besides,multiple pathsways including TGF-??Wnt?Notch?MAPK coordinate it.Polypyrimidine Tract Binding Protein 1(PTBP1)is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression.PTBP1 is now widely accepted as a multi-functional protein shuttling between nucleus and cytoplasm.Accordingly,PTB can interact with selected RNA targets,Structural elements and proteins.There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons.Besides,it is involved in RNA Polyadenylation and sability,mediates Translation Initiation.PTBP1 has been proven to be overexpressioned and multi-fuctional in various cancers,such as ovarian cancer?melanoma and glioma,but its roles in breast cancer and metastasis have not been explored.Here,we report that PTBP1 is upregulated in breast tumor samples and breast cencer cell lines tested.Silencing PTBP1 in malignant cancer cells reverses EMT program and induces cell migration and invasion ability,along with epithelial stem cell properties defined by decreased CD44high/CD24 low cell subpopulation and mammosphere-forming ability.Similarly,silencing PTBP1 represses breast tumor growth and lung metastasis in vivo.Further research revels silencing PTBP1 induces low expression of p-p38 in malignant cancer cells,we infer that PTBP1 may mediate the p38 MAPK pathway.Our findings define an important function for PTBP1 in the progression of breast cancer by orchesting EMT,and they implicate this gene product as a marker of poor prognosis in this diease.