SOX11-induced decrease in vimentin and an increase in prostate cancer cell migration attributed to cofilin activity.

SOX11 is a transcription factor in the SOX family of genes that regulate multiple cellular events by influencing the expression of key genes in developmental, physiological, and tumorigenic cells. To elucidate the role of SOX11 in prostate cancer cells, PC-3 prostate cancer cells were cloned (S6 and S9 cells) to highly express SOX11. We demonstrated that both S6 and S9 lose vimentin expression, acquiring epithelial marker proteins, which indicates the Epithelial state phenotype. S6 and S9 cells have cancer-promoting characteristics that include higher migratory properties compared with control cells. The mechanisms that are responsible for the enhanced migration are cofilin activity and keratin 18 expression. TCGA (The Cancer Genome Atlas) dataset analysis revealed that metastatic prostate cancer tumors tend to have more SOX11 gene amplification compared with primary tumors. These results suggest the tumor promotive role and epithelial protein induction of SOX11 in prostate cancer cell.

Arabidopsis NF-YB subunits LEC1 and LEC1-LIKE activate transcription by interacting with seed-specific ABRE-binding factors.

LEAFY COTYLEDON 1 (LEC1) plays vital roles in the regulation of seed maturation in Arabidopsis. LEC1 encodes a homolog of yeast HAP3 or mammalian NF-YB/CBF-A subunit of trimeric CCAAT binding factor (CBF). Among the nine paralogs of NF-YB in Arabidopsis, LEC1-LIKE (L1L) is most closely related to LEC1, and can complement the lec1 mutation when expressed under the control of the LEC1 promoter. Although the nature of the B3-type seed maturation regulators as transcription factors have been investigated, knowledge of the molecular action of LEC1 is limited. When co-expressed with NF-YC2 in the presence of ABA, we found that LEC1 or L1L, but not other NF-YBs, activated the promoter of CRUCIFERIN C (CRC), which encodes a seed storage protein. However, additional expression of an NF-YA subunit interfered with the activation. The LEC1/L1L-[NF-YC2] activation depended on ABA-response elements present in the promoter, which led to the finding that LEC1/L1L-[NF-YC2] can strongly activate the CRC promoter in the absence of ABA when co-expressed with a seed-specific ABA-response element (ABRE)-binding factor, bZIP67. Functional coupling of LEC1/L1L-[AtNF-YC2] and bZIP67 was also observed in the regulation of sucrose synthase 2 (SUS2). Immunoprecipitation experiments revealed that L1L and bZIP67 formed a protein complex in vivo. These results demonstrate a novel plant-specific mechanism for NF-Y subunit function that enables LEC1 and L1L to regulate a defined developmental network.

Inflammatory suppressive effect of prostate cancer cells with prolonged exposure to transforming growth factor ß on macrophage-differentiated cells via downregulation of prostaglandin E2.

Transforming growth factor ß1 (TGFß1) regulates a variety of cellular functions, including cell growth, apoptosis and differentiation. The aim of the current study was to investigate the alterations of phenotypic events in the long-term exposure of prostate cancer (PCa) cells to TGFß1 and its effect on macrophage-differentiated cells. The PCa cell line, PC-3, and the subclone, M1, were exposed to TGFß1 for short- or long-term periods. TGFß1 signaling was assessed by Smad3 phosphorylation, and non-canonical signaling was analyzed by quantitative polymerase chain reaction-based regulatory gene expression profiles. TGFß1-exposed PCa cells were also co-cultured with phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages as a model of the tumor microenvironment. The phosphorylation of Smad3 in the PCa cells with long-term exposure was lower than that in the PCa cells with short-term exposure. Interleukin-6 mRNA expression in the PMA-treated THP-1 macrophages was significantly downregulated by co-culture with the PCa cells with long-term exposure. Cyclooxygenase-2 expression in the long-term TGFß1-exposed PCa cells was lower than that in the control PCa cells, and the production of prostaglandin E2 (PGE2) in the long-term TGFß1-exposed PCa cells was also significantly lower. The results of the current study demonstrated that the long-term TGFß1 exposure of PCa cells induces phenotypic changes, including the downregulation of PGE2 production. This indicates that prolonged TGFß-exposed PCa cells may change the cytokine production of macrophages in the tumor microenvironment.