A previous study indicated that C–C chemokine(C–C motif)ligand 18(CCL18)is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3(PITPNM3)in breast cancer cells.The present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma(HCC).Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines.Wound-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells,and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence.The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue.Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells,whereas the upregulation of PITPNM3 significantly increased HCC cell mobility.Furthermore,inhibiting the expression of PITPNM3 suppressed the activation of Pyk2,FAK,and Src,while overexpression of PITPNM3enhanced the phosphorylation of FAK and Src in HCC cells.Besides,suppression of Pyk2 can also impair the clustering of integrin.These results imply that PITPNM3 is a vital determinant of HCC migration and invasion.
A highly dynamic development process exits within the epithelia of mammary gland,featuring morphogenetic variation during puberty,pregnancy,lactation,and regression.The identification of mammary stem cells(MaSCs)via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia.A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation.Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes,it still lacks experimental proofs whether MaSCs,the most primitive cells,are the‘seeds’of malignant transformation during most,if not all,tumorigenesis in the breast.Here,we review current knowledge of mammary epithelial hierarchy,highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells(BCSCs)along with their key molecular regulators in organ development and cancer evolution.Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer(BrCa).
