Therefore, we propose that contributes to cell invasion by regulating CD24 expression. CD24 expression. Notably, the increased adhesion of plays critical roles in the CSC self-renewal and cell adhesion of PDAC that lead to invasion and metastasis. Our findings suggest that represents a novel therapeutic target for the metastasis of pancreatic cancer. gene, located at human chromosome 11p15.5, encodes an imprinted lncRNA. is transcribed exclusively from the maternal allele, and the gene also generates an oncofetal RNA that is expressed in the developing embryo and in certain types of tumor [11, 12]. Recent evidence indicates that enhances invasion and metastasis in bladder cancer [13, 14], glioma [15], osteosarcoma [16], acute myeloid leukemia [17], breast cancer [18, 19], non-small cell lung cancer [20], gastric cancer [21], and pancreatic cancer [22], but suppresses the aggressiveness of hepatocellular carcinoma [23] and prostate cancer [24]. We recently reported that was the highest-expressed ncRNA in PANC-1 lung metastasis-derived human pancreatic cancer cells and that inhibition of decreased the lung and liver metastases of pancreatic cancer in immunodeficient mice [25]; this finding indicates that represents a novel candidate for targeted therapy against pancreatic cancer metastasis. However, the molecular mechanisms of contribution in PDAC cells remain poorly clarified. Therefore, we examined the mechanisms WDR5-0103 by which regulates PDAC metastasis, with a focus on cancer stem cells (CSCs), by using PDAC cells in which was either overexpressed or depleted. Here, Slc2a4 we show that promotes sphere formation, which indicates self-renewal ability, and invasion by regulating integrin and CD24 expression in PDAC cells. RESULTS expression in PDAC cells To determine whether is expressed heterogeneously or homogeneously in human PDAC cells, we examined expression in PANC-1 cells by using a highly sensitive hybridization technique. Under the adherent-culture condition, PANC-1 cells showed heterogeneous expression and the presence of small populations of expression was detected among the sphere cells than in cells cultured under the adherent-culture condition (Figure ?(Figure1B).1B). Numerous hybridization (Figure ?(Figure1A,1A, right panel, arrow). These results suggest that is expressed in CSC-like cells among PANC-1 cells. CSCs are responsible for tumor initiation, growth, and even metastasis [27]. We previously showed that contributes to liver and lung metastases in PANC-1 cells [25]. Thus, we hypothesized that a correlation exists between and CSCs, and we examined the mechanisms by which affects CSC phenotypes (Figure ?(Figure1C1C). Open in a separate window Figure 1 expression in PDAC cells(A) expression was analyzed by performing hybridization in PANC-1 cells. Fewer was performed using cDNA derived WDR5-0103 from adherent and 3D-cultured PANC-1 cells. ** 0.01. (C) Schematic depiction of the question addressed in this study. Results are presented as means SD from three independent experiments. contributes to sphere formation in PDAC cells To clarify the involvement of in the development of CSC characteristics, we examined self-renewal ability and CSC-marker expression in expression in and promotes sphere-formation but is not clearly involved in stemness-marker expression in PDAC cells. Open in a separate window Figure 2 contributes to sphere formation in PDAC cells(A) qRT-PCR analysis of was performed using cDNA derived from mock and 0.05, ** 0.01. (B and C) Results of sphere-formation assays showing increased and decreased sphere formation by, respectively, 0.05, ** 0.01. (D and E) qRT-PCR analysis of stemness markers was performed using cDNA derived from mock and 0.05. Results are presented as means SD from three independent experiments. CSCs possess an effective efflux pathway for anticancer drugs. Thus, we next examined whether contributes to anticancer-drug resistance in PDAC cells. We tested three commonly used anti-pancreatic cancer drugs, gemcitabine, 5-FU, and abraxane. Survival rates of the cells after addition of gemcitabine, 5-FU, and abraxane (all at 100 M) were approximately 10%, 30%, and 10%, respectively (Figure ?(Figure3A).3A). The survival rates WDR5-0103 did not differ in a statistically significant manner between mock and was not significantly different between mock and is not involved in regulating the expression of anticancer drug transporters and the resistance toward anticancer drugs in PDAC cells. Open in a separate window Figure 3.