The Wnt/beta-catenin/VASP positive feedback loop drives cell proliferation and migration in breast cancer
ONCOGENE
Authors: Li, Kai; Zhang, Jingwei; Tian, Yihao; He, Yanqi; Xu, Xiaolong; Pan, Wenting; Gao, Yang; Chen, Fangfang; Wei, Lei
Abstract
Previous studies have shown that the main function of VASP is to regulate the cytoskeleton and play an important role in promoting tumor cell metastasis. In this study, we first reveal that VASP is located in the nucleus of breast cancer cells and elucidate a Wnt/beta-catenin/VASP positive feedback loop. We identify that VASP is a target gene of Wnt/beta-catenin signaling pathway, and activation of Wnt/beta-catenin signaling pathway can significantly upregulate VASP protein expression, while upregulated VASP protein can in turn promote translocation of beta-catenin and DVL3 proteins into the nucleus. In the nucleus, VASP, DVL3, beta-catenin, and TCF4 can form VASP/DVL3/beta-catenin/TCF4 protein complex, activating Wnt/beta-catenin signaling pathway, and promoting the expression of target genes VASP, c-myc, and cyclin D1. Thus, our study reveals that there is a Wnt/beta-catenin/VASP malignant positive feedback loop in breast cancer, which promotes the proliferation and migration of breast cancer cells, and breaking this positive feedback loop may provide new strategy for breast cancer treatment.
Specific interferon tau gene-regulation networks in bovine endometrial luminal epithelial cells
THERIOGENOLOGY
Authors: Zhao, Gan; Jiang, Kangfeng; Zhang, Tao; Wu, Haichong; Qiu, Changwei; Deng, Ganzhen
Abstract
Interferon tau (IFNT) plays a critical role as a pregnancy recognition factor in early pregnancy by regulating uterine epithelial gene expression. Illuminating the relation between IFNT and pregnancy will contribute significantly to early pregnancy research in ruminants. Therefore, in this study, we treated primary bovine endometrial luminal epithelial cells (bELECs) without or with IFNT (200 ng/mL) for 6 or12 h. Subsequently, RNA sequencing (RNA-seq) technology was used to evaluate differences in gene expression. In total, 707 differentially expressed genes (DEGs) were detected. These DEGs were significantly enriched in immune-related categories or pathways, including immune system process, MHC class I protein complex, antigen processing and presentation, and graft-versus-host disease. Furthermore, an integrated regulatory network was constructed to elucidate the interactions among these DEGs. A set of candidate genes (RAC2, DVL3, PSMB9, STAT1, ISG15, JAK1, and MUC1) was identified. Upon integration of these node genes, we speculated that IFNT might upregulate MHC molecules via a JAK1-STAT1-ISG15/PSMB9 axis involved in the maintenance of a tolerant environment during early pregnancy. Our results forma foundation for dissecting the molecular mechanism of IFNT in the uterus; future studies will use these data to identify and characterize new IFNT regulatory mechanisms in the endometrium. (C) 2017 Elsevier Inc. All rights reserved.