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Mahmood Faraz, Carl Herdenberg, Camilla Holmlund, Roger Henriksson, Håkan Hedman
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors...
March 2, 2018: Journal of Biological Chemistry
Feng Mao, Baofeng Wang, Qungen Xiao, Fangling Cheng, Ting Lei, Dongsheng Guo
Gliomas are the most common intracranial tumors of the nervous system. These tumors are characterized by unlimited cell proliferation and excessive invasiveness. Despite the advances in diagnostic imaging, microneurosurgical techniques, radiation therapy, and chemotherapy, significant increases in the progression free survival of glioma patients have not been achieved. Improvements in our understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways may impact both the diagnosis and the treatment strategies for patients with gliomas...
December 15, 2017: Journal of the Neurological Sciences
Cecilia Ranhem, Gabriella Lillsunde Larsson, Håkan Hedman, David Lindquist, Mats G Karlsson, Ann-Cathrin Hellström, Ellinor Östensson, Bengt Sorbe, Kristina Hellman, Sonia Andersson
BACKGROUND: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients. METHODS: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients...
2017: PloS One
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
July 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Uzma Malik, Aneela Javed
The human leucine-rich repeats and immunoglobulin like domains (LRIG) are evolutionary conserved family of single-pass transmembrane proteins. LRIG gene family includes three members, LRIG1 (formerly LIG1), LRIG2 and LRIG3, all of which are differentially expressed in human tissues and have long been proposed to be tumor suppressors. However, recently accumulated evidence on LRIG protein expression in human cancer appears to be inconsistent with this belief, as LRIG proteins have been found to be upregulated in certain tumors...
2017: Current Cancer Drug Targets
Martin Hellström, Madelene Ericsson, Bengt Johansson, Mahmood Faraz, Fredrick Anderson, Roger Henriksson, Stefan K Nilsson, Håkan Hedman
Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice...
June 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
L Guo, W Zhang, Y Sheng, K Chen, Q Shi, P Zhang, R Zhang
OBJECTIVE: To explore the effect of LRIG3 in the development of cervical squamous cell carcinoma. MATERIALS AND METHODS: LRIG3 and epidermal growth factor receptor (EFGR) expressions were detected by immunohistochemistry. Western blot method was used to detect LRIG3 and EGFR protein expression at different time points. MTT, flow cytometry, and transwell chamber were adopted to examine the proliferation, apoptosis, and strength of invasion of Hela229 cell respectively...
2015: European Journal of Gynaecological Oncology
Samuel Kvarnbrink, Terese Karlsson, Karolina Edlund, Johan Botling, David Lindquist, Karin Jirström, Patrick Micke, Roger Henriksson, Mikael Johansson, Håkan Hedman
BACKGROUND: The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins are involved in the regulation of cellular signal transduction. LRIG1 is an endogenous inhibitor of receptor tyrosine kinases (RTKs) and an emerging tumor suppressor. In the lung epithelium, the expression of LRIG1 is downregulated by tobacco smoking, and further downregulated in lung squamous cell carcinoma. MATERIAL AND METHODS: The expression of LRIG proteins were analyzed in 347 cases of non-small cell lung cancer (NSCLC) by immunohistochemistry, and LRIG1 mRNA expression was evaluated in 807 lung cancer samples in silico in the Oncomine database...
2015: Acta Oncologica
Dongsheng Guo, Hongkuan Yang, Yang Guo, Qungen Xiao, Feng Mao, Yihu Tan, Xueyan Wan, Baofeng Wang, Ting Lei
Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3 gene is mapped to chromosome 12q13.2, a region that is frequently deleted in a subset of glioblastoma multiforme (GBM). It has been reported that perinuclear LRIG3 staining correlated with low WHO grade of glioma and better survival of the patients. However, the relationship between LRIG3 and glioma is not very clear. The purpose of this study is to demonstrate the impacts of LRIG3 on biological characteristics of glioma and its possible mechanisms...
March 15, 2015: Journal of the Neurological Sciences
Lingyang Xu, Derek M Bickhart, John B Cole, Steven G Schroeder, Jiuzhou Song, Curtis P Van Tassell, Tad S Sonstegard, George E Liu
We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3...
March 2015: Molecular Biology and Evolution
Catalina Simion, Maria Elvira Cedano-Prieto, Colleen Sweeney
The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2 and LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including receptor tyrosine and serine/threonine kinases. LRIGs have been found to both negatively (LRIG1 and LRIG3) and positively (Sma-10 and LRIG3) regulate growth factor receptor expression and signaling, although the precise molecular mechanisms by which LRIGs function are not yet understood...
2014: Endocrine-related Cancer
David Lindquist, Samuel Kvarnbrink, Roger Henriksson, Håkan Hedman
BACKGROUND: Optimal treatment decisions for cancer patients require reliable prognostic and predictive information. However, this information is inadequate in many cases. Several recent studies suggest that the leucine-rich repeats and immunoglobulin-like domains (LRIG) genes, transcripts, and proteins have prognostic implications in various cancer types. MATERIAL AND METHODS: Relevant literature was identified on PubMed using the key words lrig1, lrig2, and lrig3...
September 2014: Acta Oncologica
A K Lindström, D Hellberg
The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers...
2014: European Journal of Histochemistry: EJH
Tony Del Rio, Allison M Nishitani, Wei-Ming Yu, Lisa V Goodrich
Lrig proteins are conserved transmembrane proteins that modulate a variety of signaling pathways from worm to humans. In mammals, there are three family members - Lrig1, Lrig2, and Lrig3--that are defined by closely related extracellular domains with a similar arrangement of leucine rich repeats and immunoglobulin domains. However, the intracellular domains show little homology. Lrig1 inhibits EGF signaling through internalization and degradation of ErbB receptors. Although Lrig3 can also bind ErbB receptors in vitro, it is unclear whether Lrig2 and Lrig3 exhibit similar functions to Lrig1...
2013: PLoS Genetics
Veronica Rondahl, Camilla Holmlund, Terese Karlsson, Baofeng Wang, Mahmood Faraz, Roger Henriksson, Håkan Hedman
BACKGROUND: The leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins constitute an integral membrane protein family that has three members: LRIG1, LRIG2, and LRIG3. LRIG1 negatively regulates growth factor signaling, but little is known regarding the functions of LRIG2 and LRIG3. In oligodendroglial brain tumors, high expression of LRIG2 correlates with poor patient survival. Lrig1 and Lrig3 knockout mice are viable, but there have been no reports on Lrig2-deficient mice to date...
2013: PloS One
Hanine Rafidi, Francisco Mercado, Michael Astudillo, William H D Fry, Matthew Saldana, Kermit L Carraway, Colleen Sweeney
Lrig1 is the founding member of the Lrig family of transmembrane leucine-rich repeat proteins, which also includes Lrig2 and Lrig3. Lrig1 is a negative regulator of oncogenic receptor tyrosine kinases, including ErbB and Met receptors, and promotes receptor degradation. Lrig1 has recently emerged as both a tumor suppressor and a key regulator of epidermal and epithelial stem cell quiescence. Despite this, little is known of the mechanisms by which Lrig1 is regulated. Lrig3 was recently reported to increase ErbB receptor expression suggesting that it may function in a manner opposite to Lrig1...
July 26, 2013: Journal of Biological Chemistry
Y Wang, E J Poulin, R J Coffey
In baseball parlance, a triple threat is a person who can run, hit and throw with aplomb. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell surface protein that antagonises ERBB receptor signalling by downregulating receptor levels. Over 10 years ago, Hedman et al postulated that LRIG1 might be a tumour suppressor. Recently, Powell et al provided in vivo evidence substantiating that claim by demonstrating that Lrig1 loss in mice leads to spontaneously arising, highly penetrant intestinal adenomas...
May 14, 2013: British Journal of Cancer
Yong Qi, Lei Chang, Heng Li, Gan Yu, Wei Xiao, Ding Xia, Wei Guan, Yang Yang, Bin Lang, Kang-li Deng, Wei-min Yao, Zhang-qun Ye, Qian-yuan Zhuang
The purpose of this study was to investigate the impact of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological features of bladder cancer cell lines. The plasmids of over-expressed LRIG3 and the blank plasmid serving as control were transfected into the bladder cancer cell lines, T24, EJ and BIU-87, and the expression levels of LRIG3 mRNA and protein were detected by using real-time PCR and Western blotting. The changes in the cell cycle and apoptosis were examined by using flow cytometry...
February 2013: Journal of Huazhong University of Science and Technology. Medical Sciences
Susanne Muller, David Lindquist, Lena Kanter, Carmen Flores-Staino, Roger Henriksson, Håkan Hedman, Sonia Andersson
The incidence of cervical adenocarcinoma, which accounts for 10-20% of all cervical cancers, has increased continuously in developed countries during the last two decades, unlike squamous cell cervical carcinoma. This increasing trend, noted particularly among women under the age of 40 years, has occurred despite extensive cytological Pap smear screening. A deeper understanding of the etiology of cervical adenocarcinoma, better preventive measures and reliable prognostic markers are urgently needed. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3...
January 2013: International Journal of Oncology
Adrian K K Teo, Yusuf Ali, Kee Yew Wong, Hiram Chipperfield, Akila Sadasivam, Yogavalli Poobalan, Ee Kim Tan, Siew Tein Wang, Suman Abraham, Norihiro Tsuneyoshi, Lawrence W Stanton, N Ray Dunn
Human embryonic stem cells (hESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. We show that combining a second related ligand, BMP4, in combination with Activin A yields 15%-20% more DE as compared with Activin A alone...
April 2012: Stem Cells
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