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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...
September 7, 2016: Current Cancer Drug Targets
Hua Yang, Jun Yao, Jiangpin Yin, Xuan Wei
The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner...
May 2016: Cancer Biotherapy & Radiopharmaceuticals
Susan van Erp, Dianne M A van den Heuvel, Yuki Fujita, Ross A Robinson, Anita J C G M Hellemons, Youri Adolfs, Eljo Y Van Battum, Anna M Blokhuis, Marijn Kuijpers, Jeroen A A Demmers, Håkan Hedman, Casper C Hoogenraad, Christian Siebold, Toshihide Yamashita, R Jeroen Pasterkamp
Many guidance receptors are proteolytically cleaved by membrane-associated metalloproteases of the ADAM family, leading to the shedding of their ectodomains. Ectodomain shedding is crucial for receptor signaling and function, but how this process is controlled in neurons remains poorly understood. Here, we show that the transmembrane protein Lrig2 negatively regulates ADAM-mediated guidance receptor proteolysis in neurons. Lrig2 binds Neogenin, a receptor for repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by ADAM17 (TACE)...
December 7, 2015: Developmental Cell
Yuzhi An, Zibo Zhao, Pengju Ou, Guangchuan Wang
Somatic mutations, which are associated with a certain rate of response to targeted therapies, are ubiquitously found in human non-small cell lung cancer (NSCLC). However, it is largely unknown which group of patients may benefit from the respective treatments targeting different somatic mutations. Therefore, more effective prognostic and predictive markers are desperately needed for the treatment of NSCLC harboring different somatic mutations. The leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumor suppressor gene that belongs to the LRIG family...
November 2015: Medicine (Baltimore)
N Yokdang, J Hatakeyama, J H Wald, C Simion, J D Tellez, D Z Chang, M M Swamynathan, M Chen, W J Murphy, K L Carraway Iii, C Sweeney
LRIG1 (leucine-rich repeat and immunoglobulin-like domain containing), a member of the LRIG family of transmembrane leucine-rich repeat-containing proteins, is a negative regulator of receptor tyrosine kinase signaling and a tumor suppressor. LRIG1 expression is broadly decreased in human cancer and in breast cancer and low expression of LRIG1 has been linked to decreased relapse-free survival. Recently, low expression of LRIG1 was revealed to be an independent risk factor for breast cancer metastasis and death...
June 2, 2016: Oncogene
Nigel Fleeman, Adrian Bagust, Sophie Beale, Angela Boland, Rumona Dickson, Kerry Dwan, Marty Richardson, Yenal Dundar, Helen Davis, Lindsay Banks
The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014...
September 2015: PharmacoEconomics
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
Qungen Xiao, Yihu Tan, Yang Guo, Hongkuan Yang, Feng Mao, Ruifan Xie, Baofeng Wang, Ting Lei, Dongsheng Guo
The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family contains LRIG1, 2 and 3, encoding integral membrane proteins with an ectodomain, a transmembrane domain and a cytoplasmic tail. LRIG1 negatively regulates multiple receptor tyrosine kinases signaling including the epidermal growth factor receptor (EGFR) and is a proposed tumor suppressor. The soluble LRIG1 ectodomain is demonstrated to be shed naturally and inhibit the progression of glioma. However, little is known regarding the functions of LRIG2...
2014: PloS One
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
Nigel Fleeman, Adrian Bagust, Sophie Beale, Kerry Dwan, Rumona Dickson, Chris Proudlove, Yenal Dundar
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of pertuzumab (Roche) to submit evidence for the clinical and cost effectiveness of pertuzumab + trastuzumab + docetaxel for the treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic or locally recurrent unresectable breast cancer in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG)...
January 2015: PharmacoEconomics
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
Kedar Moharana, Lennart Zabeau, Frank Peelman, Philippe Ringler, Henning Stahlberg, Jan Tavernier, Savvas N Savvides
Leptin activates its cognate receptor (LR) to regulate body weight and metabolically costly processes, such as reproduction and immune responses. Despite such benevolent pleiotropy, leptin-mediated signaling has been implicated in autoimmune diseases and breast cancer, thereby rejuvenating interest in leptin antagonism. We present comparative biochemical and structural studies of the LR ectodomain (LRecto) in complex with wild-type and antagonist leptin variants. We show that high-affinity binding of leptin to the cytokine receptor homology 2 domain of LRecto primes interactions with the Ig-domain (LRIg) of another leptin-bound LRecto to establish a quaternary assembly...
June 10, 2014: Structure
D Lindquist, A Näsman, M Tarján, R Henriksson, T Tot, T Dalianis, H Hedman
BACKGROUND: The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent...
April 2, 2014: British Journal of Cancer
Sophie Beale, Rumona Dickson, Adrian Bagust, Michaela Blundell, Yenal Dundar, Angela Boland, Ernie Marshall, Ruth Plummer, Chris Proudlove
Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug's clinical- and cost-effectiveness for its licenced indication, to inform the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal...
December 2013: PharmacoEconomics
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
Dharanija Rao, Everardo Macias, Steve Carbajal, Kaoru Kiguchi, John DiGiovanni
STATs play crucial roles in a wide variety of biological functions, including development, proliferation, differentiation and migration as well as in cancer development. In the present study, we examined the impact of constitutive activation of Stat3 on behavior of keratinocytes, including keratinocyte stem cells (KSC) in vivo. BK5.Stat3C transgenic (Tg) mice, which express a constitutively active form of Stat3 (Stat3C) in the basal layer of the epidermis and in the bulge region KSCs exhibited a significantly reduced number of CD34+/α6 integrin+ cells compared to non-transgenic (NTg) littermates...
February 2015: Molecular Carcinogenesis
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
Mark A Badeaux, Collene R Jeter, Shuai Gong, Bigang Liu, Mahipal V Suraneni, Joyce Rundhaug, Susan M Fischer, Tao Yang, Donna Kusewitt, Dean G Tang
The current study was undertaken to investigate potential oncogenic functions of NanogP8, a tumor-specific retrogene homolog of Nanog (expressed in pluripotent cells), in transgenic animal models. To this end, human primary prostate tumor-derived NanogP8 was targeted to the cytokeratin 14 (K14) cellular compartment, and two lines of K14-NanogP8 mice were derived. The line 1 animals, expressing high levels of NanogP8, experienced perinatal lethality and developmental abnormalities in multiple organs, including the skin, tongue, eye, and thymus in surviving animals...
August 1, 2013: Cell Cycle
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