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Dae-Shik Suh, Si Eun Park, Hanyong Jin, Kangseok Lee, Jeehyeon Bae
Although endometrial cancer is the most common type of gynecological malignancy in developed countries, its molecular etiology is not well understood. Leucine-rich repeat and immunoglobulin-like domain 2 (LRIG2) is an evolutionarily conserved gene, but its functions in the endometrium are unknown. In this study, we found that LRIG2 is highly downregulated in endometrial adenocarcinoma patients and that it functions as a tumor suppressor. LRIG2 induced the mitochondrion-mediated apoptotic pathways by regulating stoichiometric balance among BCL-2 family proteins, whereby pro-survival members, MCL-1 and BCL-xL, were downregulated and pro-apoptotic BAK and BAX were upregulated...
January 23, 2018: Oncogenesis
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
Wenqi Chen, Jinhai Zhang, Huijuan Xu, Jie Dai, Xiaorong Zhang
MicroRNAs (miRNAs) are key regulators of diverse biological processes in tumor progression including melanoma. LRIG2 is reported as an oncogene in cancer, however, little is known regarding the molecular and functions of LRIG2 in melanoma. In this study, we reported that LRIG2 expression was higher in melanoma tissues and cell lines and was regulated by miR-149-5p. Furthermore, a luciferase reporter assay and rescue experiment indicated that miR-149-5p directly targeted LRIG2 by binding its 3'UTR. The overexpression of miR-149-5p significantly suppressed melanoma cell proliferation, colony formation, and promoted cell apoptosis...
2017: American Journal of Translational Research
Hong-Kuan Yang, Hao Chen, Feng Mao, Qun-Gen Xiao, Rui-Fan Xie, Ting Lei
Active angiogenesis is the basic pathological feature of glioma. Tumor angiogenesis is involved in vascular endothelial cell migration to the tumor tissue and in the formation of tube-like structures. The present study aimed to investigate the role of leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) in glioma angiogenesis. Glioma (n=50) and normal brain (n=20) tissue samples were collected from patients to detect the expression of LRIG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGF-A), and cluster of differentiation 31 (CD31) using immunohistochemistry...
October 2017: Oncology Letters
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
Lanxiang Cong, Fang Zhang, Huaihai Shang
In the present study, we explored the participation of Notch1 targeted regulation of mir-224/LRIG2 gene signal pathway in proliferation and apoptosis of cervical cancer cells. Forty-nine cases of cervical cancer lesion samples from cervical cancer patients treated in our hospital from February 2013 to February 2015 were chosen as subjects (the observation group), and cervical samples of healthy women (42 cases) during the same period were used as the control group. We determined the mRNA and protein expression of Notch1, mir-224, and LRIG2 genes...
April 2017: Oncology Letters
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
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
Burcu Bulum, Z Birsin Özçakar, Duygu Duman, Filiz Başak Cengiz, Aslı Kavaz, Berk Burgu, Esra Baskın, Nilgün Çakar, Tarkan Soygür, Mesiha Ekim, Mustafa Tekin, Fatoş Yalçınkaya
BACKGROUND: Urofacial syndrome (UFS) is characterised by congenital bladder dysfunction accompanied by a characteristic abnormal grimace upon smiling and crying. In recent years, biallelic mutations of HPSE2 and LRIG2 have been reported in UFS patients. Non-neurogenic neurogenic bladder (NNNB) has a bladder identical to UFS without typical facial features. The aim of this study was to analyse HPSE2 mutations in patients with UFS and NNNB or severe lower urinary tract dysfunction (LUTD) without abnormal facial expression...
2015: Nephron
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
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
Helen M Stuart, Neil A Roberts, Emma N Hilton, Edward A McKenzie, Sarah B Daly, Kristen D Hadfield, Jeffery S Rahal, Natalie J Gardiner, Simon W Tanley, Malcolm A Lewis, Emily Sites, Brad Angle, Cláudia Alves, Teresa Lourenço, Márcia Rodrigues, Angelina Calado, Marta Amado, Nancy Guerreiro, Inês Serras, Christian Beetz, Rita-Eva Varga, Mesrur Selcuk Silay, John M Darlow, Mark G Dobson, David E Barton, Manuela Hunziker, Prem Puri, Sally A Feather, Judith A Goodship, Timothy H J Goodship, Heather J Lambert, Heather J Cordell, Anand Saggar, Maria Kinali, Christian Lorenz, Kristina Moeller, Franz Schaefer, Aysun K Bayazit, Stefanie Weber, William G Newman, Adrian S Woolf
Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant...
April 2015: Journal of the American Society of Nephrology: JASN
Guangchuan Wang, Jie Wu, Huijuan Song
The human leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) protein has been shown to be of prognostic value in several types of human cancer, however, the expression profiles of LRIG2 have not been described in non-small cell lung cancer (NSCLC). The present study evaluated the mRNA expression of LRIG2 in tumor specimens obtained from 39 NSCLC patients by SYBR Green quantitative polymerase chain reaction and the protein expression of LRIG2 in formalin-fixed paraffin sections obtained from 116 NSCLC patients by immunohistochemistry...
August 2014: Oncology Letters
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
Yaqin Tu, Ping Yang, Jia Yang, Yuchen Xu, Fei Xiong, Qilin Yu, Weikuan Gu, Dinel Pond, Nancy Mendelsohn, Guus A M A Lachmeijer, Shu Zhang, Cong-Yi Wang
The Urofacial (Ochoa) Syndrome (UFS) is a rare autosomal recessive disorder and over 100 patients have been reported thus far. UFS is characterized by the abnormal facial expression and dysfunctional voiding. The patients show a peculiar distortion of the facial expression (grimacing as if in pain or sadness when they tried to smile or laugh) along with urinary tract infection, enuresis, vesicoureteral reflux and hydronephrosis without any underlying neurological lesion and previous urinary obstruction. Some patients are also noted with nocturnal lagophthalmos...
2014: International Journal of Clinical and Experimental Pathology
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
Dan Hellberg, Tibor Tot
BACKGROUND/AIM: Histopathological and clinical scores to predict prognosis in cervical cancer have been of limited value. In the present study a tumor marker expression score was evaluated for prognostication in early-stage cervical cancer. MATERIALS AND METHODS: The entire study population included 128 women with invasive squamous cell cervical cancer followed-up for at least 10 years. RESULTS: Expression of 12 tumor markers (epidermal growth factor receptor (EGFR), Ki-67, c-MYC, p53, p27, E-cadherin, CD44, vascular endothelial growth factor receptor (VEGF), cyclooxygenase-2 (COX2), CD4, and leucine-rich immunoglobulin-like repeats-1 (LRIG1) and LRIG2, considered relevant for cervical cancer prognostication was evaluated by immunohistochemistry...
February 2014: Anticancer Research
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