Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule that is encoded by the myelin-related gene EMP3. EMP3 is a member of the peripheral myelin protein gene family 22-kDa (PMP22), which is mainly responsible for the formation of the sheath of compact myelin.[5][6] Although the detailed functions and mechanisms of EMP3 still remain unclear, it is suggested that EMP3 is possibly epigenetically linked to certain carcinomas.
The EMP3 structure based on the 163-amino acid sequence. Four yellow helices represent four transmembrane domains.[7]
EMP3 is a protein composed of a 163-amino acid sequence, which is expressed from its gene located on the band of the 19q13.3 in the Homo sapiens chromosome.[7] EMP3 has the highest expression in the peripheral blood leukocytes compared to the expression in other body tissues.[8] The protein is characterized by 4 transmembrane domains and two N-linked glycosylation sites in the first extracellular loop.[5]
Functionedit
EMP3 is a transmembrane protein which participates in cell to cell interaction and cell proliferation.[9] Overexpression and silencing of EMP3 both interrupt the normal expression of the EMP3 gene, which induces the progression (and formation) of cancers. Based on these properties of EMP3 and the prognostic analyses on several types of tumors and cancers, EMP3 has a tumor-suppressor-like role in regulating differentiation, apoptosis and development of cancer cells. However, the detailed mechanism still needs to be investigated.[5][6][10]
Tumorgenesis and carcinogenesisedit
Primary breast carcinomasedit
The detailed functions as well as the mechanism of EMP3 in the development of various carcinomas have remained unclear.[5][6] However, it was found that the levels of expression of EMP3 mRNA have a positive correlation in primary breast carcinomas. According to the study, EMP3 mRNA has a higher level of expression in the carcinoma compared to normal breast tissues. The overexpression of EMP3 has a significant correlation with histological grade III, lymph node metastasis, and strong Her-2 expression. Additionally, the hypermethylation on the promoter region of EMP3 has appeared in about 35% of the studies breast carcinoma cases. However, higher EMP3 expression levels occur in patients with both types of breast carcinomas, regardless of the promoter regions of EMP3 being hypermethylated or unmethylated.[10]
Hepatocellular carcinoma (HCC)edit
Hepatocellular carcinoma (HCC), which is mainly caused by the chronic infections of hepatitis B virus and hepatitis C virus, become one of the major causes of cancer mortality worldwide in the recent years.[11][12] EMP3 expression in HCC tumor cells has a higher expression level than that it does in normal tissues at similar regions of the liver. It was also found that the HCC patients who have a relatively lower histological grade inversely possess a higher level of expression in EMP3. Then, the researchers found that knockdown (gene silencing) of EMP3 resulted in reduction of cell proliferation and arrest of cell cycle, which suggests a potential role of EMP3 in tumor-suppressing.[13]
Brain canceredit
EMP3 is found to play a large role in the progression of neuroblastomas and glioblastomas, which are two of the most common types of brain cancers. Both have fast carcinogenesis result in a high rate of mortality.[5][9] EMP3 is proposed as an oncogene whose overexpression in the progression correlated with glioblastoma (GBM).[9] Reduction in EMP3 expression in CD44-high GBM cell lines promotes apoptosis of the cancer cell lines and disables potential tumorigenesis.[9]
One of the signaling activation pathway involving EMP3 in the progression of glioblastoma was identified in 2016. The pathway was identified as TGF-β/Smad2/3 signaling, in which the unregulated TGF-β signaling promotes tumorigenesis in various human cells, especially CD44-high glioma cells.[9] The interaction between EMP3 and the receptor of TGF-β regulate the TGF-β/Smad2/3 signaling activation, which eventually suppresses cell proliferation and weakens tumorigenesis in glioblastoma.[9]
Clinical significanceedit
Due to the controversial effects of EMP3 on tumor suppression, the applicable treatments for certain carcinomas related to EMP3 are still unvalidated in humans.[13][14] However, some animal experiments have showed a positive result on suppressing the tumorous tissues by modifying the EMP3 gene.[13]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000142227 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000040212 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcdeAlaminos M, Dávalos V, Ropero S, Setién F, Paz MF, Herranz M, Fraga MF, Mora J, Cheung NK, Gerald WL, Esteller M (April 2005). "EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma". Cancer Research. 65 (7): 2565–71. doi:10.1158/0008-5472.CAN-04-4283. PMID 15805250.
^ abcMellai M, Piazzi A, Caldera V, Annovazzi L, Monzeglio O, Senetta R, Cassoni P, Schiffer D (2013). "Promoter hypermethylation of the EMP3 gene in a series of 229 human gliomas". BioMed Research International. 2013: 756302. doi:10.1155/2013/756302. PMC3776370. PMID 24083241.
^ abStrausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
^Taylor V, Suter U (October 1996). "Epithelial membrane protein-2 and epithelial membrane protein-3: two novel members of the peripheral myelin protein 22 gene family". Gene. 175 (1–2): 115–20. doi:10.1016/0378-1119(96)00134-5. PMID 8917086.
^ abcdefJun F, Hong J, Liu Q, Guo Y, Liao Y, Huang J, Wen S, Shen L (February 2017). "Epithelial membrane protein 3 regulates TGF-β signaling activation in CD44-high glioblastoma". Oncotarget. 8 (9): 14343–14358. doi:10.18632/oncotarget.11102. PMC5362410. PMID 27527869.
^ abZhou W, Jiang Z, Li X, Xu F, Liu Y, Wen P, Kong L, Hou M, Yu J (February 2009). "EMP3 overexpression in primary breast carcinomas is not associated with epigenetic aberrations". Journal of Korean Medical Science. 24 (1): 97–103. doi:10.3346/jkms.2009.24.1.97. PMC2650972. PMID 19270820.
^Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (March 2015). "Global cancer statistics, 2012". CA: A Cancer Journal for Clinicians. 65 (2): 87–108. doi:10.3322/caac.21262. PMID 25651787. S2CID 34813938.
^Degasperi E, Colombo M (October 2016). "Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease". The Lancet. Gastroenterology & Hepatology. 1 (2): 156–164. doi:10.1016/S2468-1253(16)30018-8. PMID 28404072.
^ abcHsieh YH, Hsieh SC, Lee CH, Yang SF, Cheng CW, Tang MJ, Lin CL, Lin CL, Chou RH (October 2015). "Targeting EMP3 suppresses proliferation and invasion of hepatocellular carcinoma cells through inactivation of PI3K/Akt pathway". Oncotarget. 6 (33): 34859–74. doi:10.18632/oncotarget.5414. PMC4741495. PMID 26472188.
^Morris LG, Chan TA (May 2015). "Therapeutic targeting of tumor suppressor genes". Cancer. 121 (9): 1357–68. doi:10.1002/cncr.29140. PMC4526158. PMID 25557041.
May 11, 2024
emp3, epithelial, membrane, protein, trans, membrane, signaling, molecule, that, encoded, myelin, related, gene, member, peripheral, myelin, protein, gene, family, pmp22, which, mainly, responsible, formation, sheath, compact, myelin, although, detailed, funct. Epithelial membrane protein 3 EMP3 is a trans membrane signaling molecule that is encoded by the myelin related gene EMP3 EMP3 is a member of the peripheral myelin protein gene family 22 kDa PMP22 which is mainly responsible for the formation of the sheath of compact myelin 5 6 Although the detailed functions and mechanisms of EMP3 still remain unclear it is suggested that EMP3 is possibly epigenetically linked to certain carcinomas EMP3IdentifiersAliasesEMP3 YMP epithelial membrane protein 3External IDsOMIM 602335 MGI 1098729 HomoloGene 1090 GeneCards EMP3Gene location Human Chr Chromosome 19 human 1 Band19q13 33Start48 321 509 bp 1 End48 330 553 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 B3 7 29 6 cMStart45 567 447 bp 2 End45 570 828 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytesynovial jointstromal cell of endometriumsmooth muscle tissuecanal of the cervixsynovial membraneright lungleft uterine tubethoracic aortaascending aortaTop expressed incalvariaadrenal glandankleexternal carotid arteryinternal carotid arterylipbelly cordbone marrowaortic valvedermisMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein bindingCellular componentintegral component of membrane plasma membrane membraneBiological processbleb assembly cell death negative regulation of cell population proliferation cell growthSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez201413732EnsemblENSG00000142227ENSMUSG00000040212UniProtP54852O35912RefSeq mRNA NM 001313905NM 001425NM 001146346NM 010129RefSeq protein NP 001300834NP 001416NP 001139818NP 034259Location UCSC Chr 19 48 32 48 33 MbChr 7 45 57 45 57 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 2 1 Tumorgenesis and carcinogenesis 2 1 1 Primary breast carcinomas 2 1 2 Hepatocellular carcinoma HCC 2 1 3 Brain cancer 3 Clinical significance 4 ReferencesStructure edit nbsp The EMP3 structure based on the 163 amino acid sequence Four yellow helices represent four transmembrane domains 7 EMP3 is a protein composed of a 163 amino acid sequence which is expressed from its gene located on the band of the 19q13 3 in the Homo sapiens chromosome 7 EMP3 has the highest expression in the peripheral blood leukocytes compared to the expression in other body tissues 8 The protein is characterized by 4 transmembrane domains and two N linked glycosylation sites in the first extracellular loop 5 Function editEMP3 is a transmembrane protein which participates in cell to cell interaction and cell proliferation 9 Overexpression and silencing of EMP3 both interrupt the normal expression of the EMP3 gene which induces the progression and formation of cancers Based on these properties of EMP3 and the prognostic analyses on several types of tumors and cancers EMP3 has a tumor suppressor like role in regulating differentiation apoptosis and development of cancer cells However the detailed mechanism still needs to be investigated 5 6 10 Tumorgenesis and carcinogenesis edit Primary breast carcinomas edit The detailed functions as well as the mechanism of EMP3 in the development of various carcinomas have remained unclear 5 6 However it was found that the levels of expression of EMP3 mRNA have a positive correlation in primary breast carcinomas According to the study EMP3 mRNA has a higher level of expression in the carcinoma compared to normal breast tissues The overexpression of EMP3 has a significant correlation with histological grade III lymph node metastasis and strong Her 2 expression Additionally the hypermethylation on the promoter region of EMP3 has appeared in about 35 of the studies breast carcinoma cases However higher EMP3 expression levels occur in patients with both types of breast carcinomas regardless of the promoter regions of EMP3 being hypermethylated or unmethylated 10 Hepatocellular carcinoma HCC edit Hepatocellular carcinoma HCC which is mainly caused by the chronic infections of hepatitis B virus and hepatitis C virus become one of the major causes of cancer mortality worldwide in the recent years 11 12 EMP3 expression in HCC tumor cells has a higher expression level than that it does in normal tissues at similar regions of the liver It was also found that the HCC patients who have a relatively lower histological grade inversely possess a higher level of expression in EMP3 Then the researchers found that knockdown gene silencing of EMP3 resulted in reduction of cell proliferation and arrest of cell cycle which suggests a potential role of EMP3 in tumor suppressing 13 Brain cancer edit EMP3 is found to play a large role in the progression of neuroblastomas and glioblastomas which are two of the most common types of brain cancers Both have fast carcinogenesis result in a high rate of mortality 5 9 EMP3 is proposed as an oncogene whose overexpression in the progression correlated with glioblastoma GBM 9 Reduction in EMP3 expression in CD44 high GBM cell lines promotes apoptosis of the cancer cell lines and disables potential tumorigenesis 9 One of the signaling activation pathway involving EMP3 in the progression of glioblastoma was identified in 2016 The pathway was identified as TGF b Smad2 3 signaling in which the unregulated TGF b signaling promotes tumorigenesis in various human cells especially CD44 high glioma cells 9 The interaction between EMP3 and the receptor of TGF b regulate the TGF b Smad2 3 signaling activation which eventually suppresses cell proliferation and weakens tumorigenesis in glioblastoma 9 Clinical significance editDue to the controversial effects of EMP3 on tumor suppression the applicable treatments for certain carcinomas related to EMP3 are still unvalidated in humans 13 14 However some animal experiments have showed a positive result on suppressing the tumorous tissues by modifying the EMP3 gene 13 References edit a b c GRCh38 Ensembl release 89 ENSG00000142227 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000040212 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c d e Alaminos M Davalos V Ropero S Setien F Paz MF Herranz M Fraga MF Mora J Cheung NK Gerald WL Esteller M April 2005 EMP3 a myelin related gene located in the critical 19q13 3 region is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma Cancer Research 65 7 2565 71 doi 10 1158 0008 5472 CAN 04 4283 PMID 15805250 a b c Mellai M Piazzi A Caldera V Annovazzi L Monzeglio O Senetta R Cassoni P Schiffer D 2013 Promoter hypermethylation of the EMP3 gene in a series of 229 human gliomas BioMed Research International 2013 756302 doi 10 1155 2013 756302 PMC 3776370 PMID 24083241 a b Strausberg RL Feingold EA Grouse LH Derge JG Klausner RD Collins FS et al December 2002 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proceedings of the National Academy of Sciences of the United States of America 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Taylor V Suter U October 1996 Epithelial membrane protein 2 and epithelial membrane protein 3 two novel members of the peripheral myelin protein 22 gene family Gene 175 1 2 115 20 doi 10 1016 0378 1119 96 00134 5 PMID 8917086 a b c d e f Jun F Hong J Liu Q Guo Y Liao Y Huang J Wen S Shen L February 2017 Epithelial membrane protein 3 regulates TGF b signaling activation in CD44 high glioblastoma Oncotarget 8 9 14343 14358 doi 10 18632 oncotarget 11102 PMC 5362410 PMID 27527869 a b Zhou W Jiang Z Li X Xu F Liu Y Wen P Kong L Hou M Yu J February 2009 EMP3 overexpression in primary breast carcinomas is not associated with epigenetic aberrations Journal of Korean Medical Science 24 1 97 103 doi 10 3346 jkms 2009 24 1 97 PMC 2650972 PMID 19270820 Torre LA Bray F Siegel RL Ferlay J Lortet Tieulent J Jemal A March 2015 Global cancer statistics 2012 CA A Cancer Journal for Clinicians 65 2 87 108 doi 10 3322 caac 21262 PMID 25651787 S2CID 34813938 Degasperi E Colombo M October 2016 Distinctive features of hepatocellular carcinoma in non alcoholic fatty liver disease The Lancet Gastroenterology amp Hepatology 1 2 156 164 doi 10 1016 S2468 1253 16 30018 8 PMID 28404072 a b c Hsieh YH Hsieh SC Lee CH Yang SF Cheng CW Tang MJ Lin CL Lin CL Chou RH October 2015 Targeting EMP3 suppresses proliferation and invasion of hepatocellular carcinoma cells through inactivation of PI3K Akt pathway Oncotarget 6 33 34859 74 doi 10 18632 oncotarget 5414 PMC 4741495 PMID 26472188 Morris LG Chan TA May 2015 Therapeutic targeting of tumor suppressor genes Cancer 121 9 1357 68 doi 10 1002 cncr 29140 PMC 4526158 PMID 25557041 Retrieved from https en wikipedia org w index php title EMP3 amp oldid 1171092153, wikipedia, wiki, book, books, library,
