Keratin 18 induces proliferation, migration, and invasion in gastric cancer via the MAPK signalling pathway
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
Authors: Wang, Peng-Bin; Chen, Yan; Ding, Guang-Rong; Du, Hong-Wei; Fan, Hong-Yan
Abstract
Purpose Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. Methods The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC-specific processes was investigated. Results Keratin 18 expression was shown to be up-regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Conclusions Keratin 18 plays a cancer-promoting role and might be a potential therapeutic target in the treatment of GC.
Human trophectoderm cells are not yet committed
HUMAN REPRODUCTION
Authors: De Paepe, Caroline; Cauffman, Greet; Verloes, An; Sterckx, Johan; Devroey, Paul; Tournaye, Herman; Liebaers, Inge; Van de Velde, Hilde
Abstract
Are human trophectoderm (TE) cells committed or still able to develop into inner cell mass (ICM) cells? Human full blastocyst TE cells still have the capacity to develop into ICM cells expressing the pluripotency marker NANOG, thus they are not yet committed. Human Day 5 full blastocyst TE cells express the pluripotency markers POU5F1, SOX2 and SALL4 as well as the TE markers HLA-G and KRT18 but not yet CDX2, therefore their developmental direction may not yet be definite. The potency of human blastocyst TE cells was investigated by determining their in vitro capacity to develop into a blastocyst with ICM cells expressing NANOG; TE cells were isolated either by aspiration under visual control or after labeling with fluorescent 594-wheat germ agglutinin. Further on, aspirated TE cells were also labeled with fluorescent PKH67 and repositioned in the center of the original embryo. Human preimplantation embryos were used for research after obtaining informed consent from IVF patients. The experiments were approved by the Local Ethical Committee and the oBelgian Federal Committee on medical and scientific research on embryos in vitro'. Outer cells were isolated and reaggregated by micromanipulation. Reconstituted embryos were analyzed by immunocytochemistry. Isolated and reaggregated TE cells from full human blastocysts are able to develop into blastocysts with ICM cells expressing the pluripotency marker NANOG. Moreover, the majority of the isolated TE cells which were repositioned in the center of the embryo do not sort back to their original position but integrate within the ICM and start to express NANOG. Owing to legal and ethical restrictions, manipulated human embryos cannot be transferred into the uterus to determine their totipotent capacity. The definitive demonstration that embryos reconstructed with TE cells are a source of pluripotent cells is to obtain human embryonic stem cell olike' line(s), which will allow full characterization of the cells. Our finding has important implications in reproductive medicine and stem cell biology because TE cells have a greater developmental potential than assumed previously. Scientific Research FoundationuFlanders (FWO-Vlaanderen) and Research Council (OZR) of the Vrije Universiteit Brussel. None of the authors declared a conflict of interest.