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Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.

Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develop a potential therapeutic treatment based on the pathogenesis and mechanism of Endometriosis. Our preliminary data showed that the expression of estrogen receptor β (ERβ) was significantly increased, while ERα was significantly decreased, in endometriotic cells compared to normal endometrial cells. Further investigation showed that betulinic acid (BA) treatment suppressed ERβ expression through epigenetic modification on the ERβ promoter, while had no effect on ERα expression. In addition, BA treatment suppresses ERβ target genes, including superoxide dismutase 2 (SOD2), nuclear respiratory factor-1 (NRF1), cyclooxygenase 2 (COX2), and matrix metalloproteinase-1 (MMP1), subsequently increasing oxidative stress, triggering mitochondrial dysfunction, decreasing elevated proinflammatory cytokines, and eventually suppressing endometriotic cell proliferation, mimicking the effect of ERβ knockdown. On the other hand, gain of ERβ by lentivirus infection in normal endometrial cells resulted in increased cell proliferation and proinflammatory cytokine release, while BA treatment diminished this effect through ERβ suppression with subsequent oxidative stress and apoptosis. Our results indicate that ERβ may be a major driving force for the development of endometriosis, while BA inhibits Endometriosis through specific suppression of the ERβ signaling pathway. This study provides a novel therapeutic strategy for endometriosis treatment through BA-mediated ERβ suppression.

Background: Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disease that is caused by partial ferrochelatase (FECH) deficiency because of a genetic mutation in the FECH gene. Objectives: The aim of this study was to investigate the genetic mechanism of EPP in a Chinese family. Methods: Clinical physical examination, laboratory testing, and medical history tracking were performed for phenotyping. The FECH gene was sequenced for genotyping. Results: The proband presented EPP with severe liver dysfunction. A novel nonsense mutation of c.910 C>T in the FECH gene, resulting in p.Arg304Ter, was identified in the proband as well as her symptomatic mother, aunt, and asymptomatic male cousin. The proband and her living family members, except the asymptomatic male cousin, carried the alleles IVS 3-48C and IVS 1-23T on the FECH gene. The mutation of c.910 C>T in the FECH gene presented its heterozygous autosomal dominant inherent clinical manifestations, only in the presence of the heterozygous alleles IVS 3-48C and IVS 1-23T. The frequencies of the alleles IVS 3-48C and IVS 1-23T were 30.8% and 27.9% in a northeast Chinese Han population, respectively. Conclusions: A new nonsense mutation of c.910 C>T was identified in the FECH gene, which expressed EPP with severe liver dysfunction when it was co-inherited with the heterozygous alleles IVS 3-48C and IVS 1-23T, in a Chinese family.