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Zhenzhen Chen, Junpei Wang, Weili Yang, Ji Chen, Yuhong Meng, Biaoqi Feng, Yujing Chi, Bin Geng, Yong Zhou, Qinghua Cui, Jichun Yang
FAM3C, a member of FAM3 gene family, has been shown to improve insulin resistance and hyperglycemia in obese mice. This study further determined whether FAM3C functions as a hepatokine to suppress hepatic gluconeogenesis of type 1 diabetic mice. In STZ-induced type 1 diabetic mouse liver, the FAM3C-HSF1-CaM signaling axis was repressed. Hepatic FAM3C overexpression activated HSF1-CaM-Akt pathway to repress gluconeogenic gene expression and ameliorate hyperglycemia of type 1 diabetic mice. Moreover, hepatic HSF1 overexpression also activated CaM-Akt pathway to repress gluconeogenic gene expression and improve hyperglycemia of type 1 diabetic mice...
December 1, 2017: Oncotarget
Zhang Xiaoyan, Weili Yang, Junpei Wang, Yuhong Meng, Youfei Guan, Jichun Yang
Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health issues worldwide. The Family with sequence similarity 3 (FAM3) gene family consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D, respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate steatosis and hyperglycemia in obese diabetic mice...
December 5, 2017: Metabolism: Clinical and Experimental
Yuan Hu, Li-Jun Tan, Xiang-Ding Chen, Zhen Liu, Shi-Shi Min, Qin Zeng, Hui Shen, Hong-Wen Deng
Context: Genome-wide association studies (GWASs) have been successful in identifying loci associated with osteoporosis and obesity. However, the findings just explain a small fraction of the total genetic variance. Objective: The aim of this study was to identify novel pleiotropic genes important in osteoporosis and obesity. Design and Setting: A pleiotropic conditional false discovery rate (cFDR) method was applied to three independent GWAS summary statistics of femoral neck bone mineral density (FN BMD), body mass index (BMI) and waist-hip ratio (WHR)...
November 14, 2017: Journal of Clinical Endocrinology and Metabolism
Maria Kral, Christoph Klimek, Betül Kutay, Gerald Timelthaler, Thomas Lendl, Benjamin Neuditschko, Christopher Gerner, Maria Sibilia, Agnes Csiszar
The interleukin-like epithelial-to-mesenchymal transition (EMT) inducer (ILEI)/FAM3C is a member of the highly homologous FAM3 family and is essential for EMT and metastasis formation. It is upregulated in several cancers, and its altered subcellular localization strongly correlates with poor survival. However, the mechanism of ILEI action, including the structural requirements for ILEI activity, remains elusive. Here, we show that ILEI formed both monomers and covalent dimers in cancer cell lines and in tumors...
October 2017: FEBS Journal
Anna M Jansson, Agnes Csiszar, Joachim Maier, Ann-Christin Nyström, Elisabeth Ax, Patrik Johansson, Lovisa Holmberg Schiavone
Production and secretion of pro-metastatic proteins is a feature of many tumor cells. The FAM3C interleukin-like epithelial-to-mesenchymal-transition (EMT) inducer (ILEI) has been shown to be strongly up-regulated in several cancers and to be essential for tumor formation and metastasis in epithelial cells, correlating with a significant decrease in overall survival in colon and breast cancer patients. ILEI has been seen to interact with the γ-secretase presenilin 1 subunit (PS1). However, not much is known about the mechanism-of-action or the detailed ILEI structure...
September 15, 2017: Journal of Biological Chemistry
Ken Noguchi, Annamarie C Dalton, Breege V Howley, Buckley J McCall, Akihiro Yoshida, J Alan Diehl, Philip H Howe
ILEI (FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. Initially, we found that ILEI mRNA is highly expressed in melanoma metastases but not in primary tumors, suggesting that ILEI contributes to the malignant properties of melanoma. While melanoma is not an epithelial cell-derived tumor and does not undergo a traditional EMT, melanoma undergoes a similar process known as phenotype switching in which high (micropthalmia-related transcription factor) MITF expressing (MITF-high) proliferative cells switch to a low expressing (MITF-low) invasive state...
2017: PloS One
Zhenzhen Chen, Liwei Ding, Weili Yang, Junpei Wang, Liming Chen, Yongsheng Chang, Bin Geng, Qinghua Cui, Youfei Guan, Jichun Yang
FAM3C is a member of the family with sequence similarity 3 (FAM3) gene family, and this study determined its role and mechanism in regulation of hepatic glucose/lipid metabolism. In obese diabetic mice, FAM3C expression was reduced in the liver, and hepatic FAM3C restoration improved insulin resistance, hyperglycemia, and fatty liver. FAM3C overexpression increased the expression of heat shock factor 1 (HSF1), calmodulin (CaM), and phosphorylated protein kinase B (Akt) and reduced that of gluconeogenic and lipogenic genes in diabetic mouse livers with the suppression of gluconeogenesis and lipid deposition...
May 2017: Diabetes
Ameya Bendre, Kalman G Büki, Jorma A Määttä
Fam3c, a cytokine-like protein, is a member of the Fam3 family (family with sequence similarity 3) and has been implicated to play a crucial role in Epithelial-to- mesenchymal transition (EMT) and subsequent metastasis during cancer progression. A few independent genome-wide association studies on different population cohorts predicted the gene locus of Fam3c to be associated with bone mineral density and fractures. In this study, we examined the role of Fam3c during osteoblast differentiation. Fam3c was found to be expressed during osteogenic differentiation of both primary bone marrow stromal cells and MC3T3-E1 pre-osteoblasts...
January 2017: Differentiation; Research in Biological Diversity
Yanan Sun, Xiaopeng Jia, Qiang Gao, Xing Liu, Lianguo Hou
Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin-like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF-β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS-440-010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression...
January 2017: IUBMB Life
Lei Liu, Naoki Watanabe, Hiroyasu Akatsu, Masaki Nishimura
Decrease in brain amyloid-β (Aβ) accumulation is a leading strategy for treating Alzheimer's disease (AD). However, the intrinsic mechanism of the regulation of brain Aβ production is largely unknown. Previously, we reported that ILEI (also referred to as FAM3C) binds to the γ-secretase complex and suppresses Aβ production without inhibiting γ-secretase activity. In this study, we examined ILEI expression in mouse brain using immunohistochemistry and subcellular fractionation. Brain ILEI showed widespread expression in neurons and ependymal cells but not in glial and vascular endothelial cells...
August 25, 2016: Neuroscience
Jorma A Määttä, Ameya Bendre, Mervi Laanti, Kalman G Büki, Pia Rantakari, Päivi Tervola, Johanna Saarimäki, Matti Poutanen, Pirkko Härkönen, Kalervo Väänänen
Fam3c, a cytokine-like growth factor, has been suggested to have a role in epithelial-to-mesenchymal transition (EMT), tumor growth and metastasis. A single-nucleotide polymorphism affecting bone mineral density has been found in the first intron of the Fam3c gene in a study analyzing an Asian population cohort. Other independent studies on different population cohorts have found the fam3c locus to be associated with bone mineral density and fractures. In order to investigate the role of Fam3c in bone biology, we have generated a Fam3c knock-out (KO) mouse strain...
2016: BoneKEy Reports
Nils Halberg, Caitlin A Sengelaub, Kristina Navrazhina, Henrik Molina, Kunihiro Uryu, Sohail F Tavazoie
Enhanced secretion of tumorigenic effector proteins is a feature of malignant cells. The molecular mechanisms underlying this feature are poorly defined. We identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and overexpressed in metastatic breast, melanoma, and colon cancers. Biochemical, molecular, and cell-biological studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3, which facilitates Golgi extension and enhanced vesicular release...
March 14, 2016: Cancer Cell
Xinjian Peng, Enquan Xu, Weiwei Liang, Xiaolei Pei, Dixin Chen, Danfeng Zheng, Yang Zhang, Can Zheng, Pingzhang Wang, Shaoping She, Yan Zhang, Jing Ma, Xiaoning Mo, Yingmei Zhang, Dalong Ma, Ying Wang
The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages...
May 1, 2016: Journal of Cell Science
Alessandra Chesi, Jonathan A Mitchell, Heidi J Kalkwarf, Jonathan P Bradfield, Joan M Lappe, Shana E McCormack, Vicente Gilsanz, Sharon E Oberfield, Hakon Hakonarson, John A Shepherd, Andrea Kelly, Babette S Zemel, Struan F A Grant
Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health...
September 1, 2015: Human Molecular Genetics
Adam A Kraya, Shengfu Piao, Xiaowei Xu, Gao Zhang, Meenhard Herlyn, Phyllis Gimotty, Beth Levine, Ravi K Amaravadi, David W Speicher
Macroautophagy, a catabolic process of cellular self-digestion, is an important tumor cell survival mechanism and a potential target in antineoplastic therapies. Recent discoveries have implicated autophagy in the cellular secretory process, but potential roles of autophagy-mediated secretion in modifying the tumor microenvironment are poorly understood. Furthermore, efforts to inhibit autophagy in clinical trials have been hampered by suboptimal methods to quantitatively measure tumor autophagy levels. Here, we leveraged the autophagy-based involvement in cellular secretion to identify shed proteins associated with autophagy levels in melanoma...
2015: Autophagy
Lei Zhang, Hyung Jin Choi, Karol Estrada, Paul J Leo, Jian Li, Yu-Fang Pei, Yinping Zhang, Yong Lin, Hui Shen, Yao-Zhong Liu, Yongjun Liu, Yingchun Zhao, Ji-Gang Zhang, Qing Tian, Yu-ping Wang, Yingying Han, Shu Ran, Rong Hai, Xue-Zhen Zhu, Shuyan Wu, Han Yan, Xiaogang Liu, Tie-Lin Yang, Yan Guo, Feng Zhang, Yan-fang Guo, Yuan Chen, Xiangding Chen, Lijun Tan, Lishu Zhang, Fei-Yan Deng, Hongyi Deng, Fernando Rivadeneira, Emma L Duncan, Jong Young Lee, Bok Ghee Han, Nam H Cho, Geoffrey C Nicholson, Eugene McCloskey, Richard Eastell, Richard L Prince, John A Eisman, Graeme Jones, Ian R Reid, Philip N Sambrook, Elaine M Dennison, Patrick Danoy, Laura M Yerges-Armstrong, Elizabeth A Streeten, Tian Hu, Shuanglin Xiang, Christopher J Papasian, Matthew A Brown, Chan Soo Shin, André G Uitterlinden, Hong-Wen Deng
Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5...
April 1, 2014: Human Molecular Genetics
Seok Jin Kim, Insuk Sohn, In-Gu Do, Sin Ho Jung, Young Hyeh Ko, Hae Yong Yoo, Soonmyung Paik, Won Seog Kim
We performed the whole genome cDNA-mediated annealing, selection and ligation assay with 164 formalin-fixed paraffin-embedded (FFPE) tumor samples to develop robust prognostic gene expression profiles in patients with diffuse large B cell lymphoma. The prognostic gene expression profiles were developed and validated by a gradient lasso and leave-one-out cross-validation process. We identified a set of genes whose expression provided prognostic indicators from whole data set (PRKCDBP, CASP10, FAM3C, KCNK12, MAN1A2, PRND, RAB1A, TMEM39B, SLC6A6, MMP12, FEM1B, C3orh37, RBP1, HK1, LOC400464, KIAA0746, and SLC25A23)...
March 2014: Annals of Hematology
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No abstract text is available yet for this article.
2012: BoneKEy Reports
Jichun Yang, Youfei Guan
Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as well as liver-related morbidity and mortality worldwide. NAFLD is also associated with increased risk of cardiovascular diseases, hyperlipidemia, and type 2 diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members designated FAM3A, FAM3B, FAM3C, and FAM3D, respectively...
August 2013: Journal of Gastroenterology and Hepatology
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