Therefore, synergistically overexpression of KLF4 and inhibition of TGFb pathway will provide a novel approach in the developing new therapeutic drugs for the treatment of ovarian cancers. In summary, this is the first report showing that KLF4 functions as a tumor suppressor by inhibiting cell proliferation, migration and invasion in ovarian cancer cells through attenuating TGFbinduced EMT. The endoplasmic reticulum is a membranous organelle where Pancuronium dibromide proteins targeted for secretion or for the plasma membrane are folded and processed. Physiological conditions that impose large amounts of proteins in the ER, as for example, the production of insulin by pancreatic b-cells, may represent a challenge to the ER folding capacity. The Unfolded Protein Response is a homeostatic mechanism that attempts to balance the load of incoming proteins into the ER to its folding Folinic acid calcium salt pentahydrate capacity, to avoid the accumulation of toxic misfolded proteins, which otherwise would cause ER stress. In higher eukaryotes, the UPR has three signaling branches triggered by different ER transmembrane proteins: protein kinase -like ER kinase, activating transcription factor 6 and Inositol-requiring enzyme 1. Ire1 is conserved across all eukaryotes, presenting a luminal domain that detects the accumulation of misfolded proteins in the ER lumen, and a cytoplasmic domain with kinase and RNase activities that trigger downstream signaling. During ER stress, Ire1 is activated and catalyzes the unconventional splicing of an intron from X-box binding protein 1 mRNA or from its functional yeast homolog Hac1. This Ire1 mediated unconventional splicing event causes a frameshift during the translation of Xbp1 mRNA that introduces a new C-terminus with a potent trans-activation domain, generating an effective transcription factor. In addition to splicing of Xbp1 mRNA, Ire1 also cleaves a variety of mRNAs, mostly encoding proteins with signal peptide/ transmembrane domains that would represent an additional challenge to the ER folding machinery under ER stress. This mechanism was named RIDD and was also described in mammalian cells and in the fission yeast S. pombe. RIDD seems to be particularly important in cells undergoing very strong ER stress. The mechanism of targeting of a specific mRNA to RIDD seems to rely mostly on the existence of a signal peptide in its respective protein; the deletion of the signal peptide from known RIDD targets prevents their degradation and conversely, addition of a signal peptide to GFP is sufficient to promote the degradation of its mRNA by RIDD. One interesting exception is the mRNA encoding Smt3, a homologue of SUMO, which is cleaved by RIDD although it does not have a signal peptide in its sequence. Xbp1 also does not have a signal peptide in its 
sequence and the mechanism of recruitment of the Xbp1 mRNA to the ER membrane is still unclear. Moreover, it seems that the mechanisms of recruitment to the ER membrane of Xbp1 mRNA in mammals and Hac1 mRNA in yeast are quite different. In yeast cells with no ER stress, the mRNA of unspliced Hac1 is found mostly in the cytoplasm, in association with stalled ribosomes. Upon ER stress, Hac1 mRNA is recruited to Ire1 clusters in the ER membrane, in a process that depends on a bipartite element present at the 39 untranslated region of the Hac1 mRNA. In contrast, ER membrane localization of mammalian Xbp1 is independent of the 39 untranslated region of Xbp1. Instead, the mRNA of Xbp1unspliced is translated under normal conditions and originates a polypeptide that associates with the membrane of the ER through two hydrophobic regions.