Skip to main content
SpringerLink
Log in

Functional importance of lysyl oxidase family propeptide regions

  • Review
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

The lysyl oxidase family of proteins is primarily known for its critical role in catalyzing extracellular oxidative deamination of hydroxylysine and lysine residues in collagens, and lysine residues in elastin required for connective tissue structure and function. Lysyl oxidases have additional important biological functions in health and disease. While the enzyme domains are highly conserved, the propeptide regions are less uniform, and have biological activity, some of which are independent of their respective enzymes. This review summarizes what has been published regarding the functions of the propeptide regions of this family of proteins in the context of extracellular matrix biosynthesis, fibrosis and cancer biology. Although much has been learned, there is a need for greater attention to structure/function relationships and mechanisms to more fully understand these multifunctional proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bais MV, Nugent MA, Stephens DN, Sume SS, Kirsch KH, Sonenshein GE, Trackman PC (2012) Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts. PLoS One 7:e31188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bais MV, Ozdener GB, Sonenshein GE, Trackman PC (2015) Effects of tumor-suppressor lysyl oxidase propeptide on prostate cancer xenograft growth and its direct interactions with DNA repair pathways. Oncogene 34:1928–1937

    Article  CAS  PubMed  Google Scholar 

  • Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Brechot N, Nasciutti L, Barret A, Teillon J, Guillon E, Etienne E, Caron M, Joubert-Caron R, Monnot C, Ruggiero F, Muller L, Germain S (2011) Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane. Blood 118:3979–3989

    Article  CAS  PubMed  Google Scholar 

  • Borel A, Eichenberger D, Farjanel J, Kessler E, Gleyzal C, Hulmes DJ, Sommer P, Font B (2001) Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1. J Biol Chem 276:48944–48949

    Article  CAS  PubMed  Google Scholar 

  • Bu M, Li L, Zhang Y, Xu Y, An S, Hou F, Jie X (2014) Lysyl oxidase genetic variants affect gene expression in cervical cancer. DNA Cell Biol 33:787–792

    Article  CAS  PubMed  Google Scholar 

  • Chang J, Lucas MC, Leonte LE, Garcia-Montolio M, Singh LB, Findlay AD, Deodhar M, Foot JS, Jarolimek W, Timpson P, Erler JT, Cox TR (2017) Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer. Oncotarget 8:26066–26078

    PubMed  PubMed Central  Google Scholar 

  • Contente S, Kenyon K, Rimoldi D, Friedman RM (1990) Expression of gene rrg is associated with reversion of NIH 3T3 transformed by LTR-c-H-ras. Science 249:796–798

    Article  CAS  PubMed  Google Scholar 

  • Cronshaw AD, Fothergill-Gilmore LA, Hulmes DJ (1995) The proteolytic processing site of the precursor of lysyl oxidase. Biochem J 306(Pt 1):279–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuevas EP, Moreno-Bueno G, Canesin G, Santos V, Portillo F, Cano A (2014) LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition. Biol Open 3:129–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuevas EP, Eraso P, Mazon MJ, Santos V, Moreno-Bueno G, Cano A, Portillo F (2017) LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Sci Rep 7:44988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Donato M, Petrillo M, Martinelli E, Filippetti F, Zannoni GF, Scambia G, Gallo D (2017) Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous ovarian cancer. Gynecol Oncol 146:170–178

    Article  PubMed  Google Scholar 

  • El-Hallous E, Sasaki T, Hubmacher D, Getie M, Tiedemann K, Brinckmann J, Batge B, Davis EC, Reinhardt DP (2007) Fibrillin-1 interactions with fibulins depend on the first hybrid domain and provide an adaptor function to tropoelastin. J Biol Chem 282:8935–8946

    Article  CAS  PubMed  Google Scholar 

  • Eliades A, Papadantonakis N, Bhupatiraju A, Burridge KA, Johnston-Cox HA, Migliaccio AR, Crispino JD, Lucero HA, Trackman PC, Ravid K (2011) Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase. J Biol Chem 286:27630–27638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, Le QT, Chi JT, Jeffrey SS, Giaccia AJ (2006) Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440:1222–1226

    Article  CAS  PubMed  Google Scholar 

  • Ezzoukhry Z, Henriet E, Piquet L, Boye K, Bioulac-Sage P, Balabaud C, Couchy G, Zucman-Rossi J, Moreau V, Saltel F (2016) TGF-beta1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking. Eur J Cell Biol 95:503–512

    Article  CAS  PubMed  Google Scholar 

  • Finney J, Moon HJ, Ronnebaum T, Lantz M, Mure M (2014) Human copper-dependent amine oxidases. Arch Biochem Biophys 546:19–32

    Article  CAS  PubMed  Google Scholar 

  • Fogelgren B, Polgar N, Szauter KM, Ujfaludi Z, Laczko R, Fong KS, Csiszar K (2005) Cellular fibronectin binds to lysyl oxidase with high affinity and is critical for its proteolytic activation. J Biol Chem 280:24690–24697

    Article  CAS  PubMed  Google Scholar 

  • Fraga A, Ribeiro R, Coelho A, Vizcaino JR, Coutinho H, Lopes JM, Principe P, Lobato C, Lopes C, Medeiros R (2017) Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer. BMC Urol 17:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Friesenhengst A, Pribitzer-Winner T, Schreiber M (2014) Association of the G473A polymorphism and expression of lysyl oxidase with breast cancer risk and survival in European women: a hospital-based case-control study. PLoS One 9:e105579

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao X, Zhang S, Zhu Z (2015) Lysyl oxidase rs1800449 polymorphism and cancer risk among Asians: evidence from a meta-analysis and a case-control study of colorectal cancer. Mol Gen Genomics 290:23–28

    Article  CAS  Google Scholar 

  • Grimsby JL, Lucero HA, Trackman PC, Ravid K, Kagan HM (2010) Role of lysyl oxidase propeptide in secretion and enzyme activity. J Cell Biochem 111:1231–1243

    Article  CAS  PubMed  Google Scholar 

  • Guo Y, Pischon N, Palamakumbura AH, Trackman PC (2007) Intracellular distribution of the lysyl oxidase propeptide in osteoblastic cells. Am J Physiol Cell Physiol 292:C2095–C2102

    Article  CAS  PubMed  Google Scholar 

  • Hamalainen ER, Jones TA, Sheer D, Taskinen K, Pihlajaniemi T, Kivirikko KI (1991) Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3-31.2. Genomics 11:508–516

    Article  CAS  PubMed  Google Scholar 

  • Han S, Feng S, Yuan G, Dong T, Gao D, Liang G, Wei X (2014) Lysyl oxidase genetic variants and the prognosis of glioma. APMIS 122:200–205

    Article  CAS  PubMed  Google Scholar 

  • Horiguchi M, Inoue T, Ohbayashi T, Hirai M, Noda K, Marmorstein LY, Yabe D, Takagi K, Akama TO, Kita T, Kimura T, Nakamura T (2009) Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase. Proc Natl Acad Sci U S A 106:19029–19034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang G, Zhang Y, Kim B, Ge G, Annis DS, Mosher DF, Greenspan DS (2009) Fibronectin binds and enhances the activity of bone morphogenetic protein 1. J Biol Chem 284:25879–25888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Igoucheva O, Alexeev V, Halabi CM, Adams SM, Stoilov I, Sasaki T, Arita M, Donahue A, Mecham RP, Birk DE, Chu ML (2015) Fibulin-4 E57K knock-in mice recapitulate cutaneous, vascular and skeletal defects of recessive cutis Laxa 1B with both elastic fiber and collagen fibril abnormalities. J Biol Chem 290:21443–21459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeay S, Pianetti S, Kagan HM, Sonenshein GE (2003) Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. Mol Cell Biol 23:2251–2263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kadler KE, Hojima Y, Prockop DJ (1987) Assembly of collagen fibrils de novo by cleavage of the type I pC-collagen with procollagen C-proteinase. Assay of critical concentration demonstrates that collagen self-assembly is a classical example of an entropy-driven process. J Biol Chem 262:15696–15701

    CAS  PubMed  Google Scholar 

  • Kagan HM, Trackman PC (1991) Properties and function of lysyl oxidase. Am J Respir Cell Mol Biol 5:206–210

    Article  CAS  PubMed  Google Scholar 

  • Kaneda A, Wakazono K, Tsukamoto T, Watanabe N, Yagi Y, Tatematsu M, Kaminishi M, Sugimura T, Ushijima T (2004) Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. Cancer Res 64:6410–6415

    Article  CAS  PubMed  Google Scholar 

  • Kenyon K, Contente S, Trackman PC, Tang J, Kagan HM, Friedman RM (1991) Lysyl oxidase and rrg messenger RNA. Science 253:802

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Park S, Kim Y (2014) Alternative promoter activation leads to the expression of a novel human lysyl oxidase variant that functions as an amine oxidase. Int J Mol Med 34:894–899

    Article  PubMed  Google Scholar 

  • Kuivaniemi H, Korhonen RM, Vaheri A, Kivirikko KI (1986) Deficient production of lysyl oxidase in cultures of malignantly transformed human cells. FEBS Lett 195:261–264

    Article  CAS  PubMed  Google Scholar 

  • Le Calve B, Griveau A, Vindrieux D, Marechal R, Wiel C, Svrcek M, Gout J, Azzi L, Payen L, Cros J, de la Fouchardiere C, Dubus P, Guitton J, Bartholin L, Bachet JB, Bernard D (2016) Lysyl oxidase family activity promotes resistance of pancreatic ductal adenocarcinoma to chemotherapy by limiting the intratumoral anticancer drug distribution. Oncotarget 7:32100–32112

    Article  PubMed  PubMed Central  Google Scholar 

  • Li W, Nellaiappan K, Strassmaier T, Graham L, Thomas KM, Kagan HM (1997) Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc Natl Acad Sci U S A 94:12817–12822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Gu X, Ma Y, Calicchio ML, Kong D, Teng YD, Yu L, Crain AM, Vartanian TK, Pasqualini R, Arap W, Libermann TA, Snyder EY, Sidman RL (2010) Nna1 mediates Purkinje cell dendritic development via lysyl oxidase propeptide and NF-kappaB signaling. Neuron 68:45–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Zhao Y, Gao J, Pawlyk B, Starcher B, Spencer JA, Yanagisawa H, Zuo J, Li T (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet 36:178–182

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Zhao Y, Pawlyk B, Damaser M, Li T (2006) Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol 168:519–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Lv B, He Z, Zhou Y, Han C, Shi G, Gao R, Wang C, Yang L, Song H, Yuan W (2012) Lysyl oxidase polymorphisms and susceptibility to osteosarcoma. PLoS One 7:e41610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu N, Cox TR, Cui W, Adell G, Holmlund B, Ping J, Jarlsfelt I, Erler JT, Sun XF (2017) Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients. Oncotarget 8:60015–60024

    PubMed  Google Scholar 

  • Lopez-Jimenez AJ, Basak T, Vanacore RM (2017). Proteolytic processing of Lysyl oxidase like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV. J Biol Chem, (In Press)

  • Lugassy J, Zaffryar-Eilot S, Soueid S, Mordoviz A, Smith V, Kessler O, Neufeld G (2012) The enzymatic activity of lysyl oxidas-like-2 (LOXL2) is not required for LOXL2-induced inhibition of keratinocyte differentiation. J Biol Chem 287:3541–3549

    Article  CAS  PubMed  Google Scholar 

  • Mariani TJ, Trackman PC, Kagan HM, Eddy RL, Shows TB, Boyd CD, Deak SB (1992) The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene). Matrix 12:242–248

    Article  CAS  PubMed  Google Scholar 

  • Maruhashi T, Kii I, Saito M, Kudo A (2010) Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. J Biol Chem 285:13294–13303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min C, Yu Z, Kirsch KH, Zhao Y, Vora SR, Trackman PC, Spicer DB, Rosenberg L, Palmer JR, Sonenshein GE (2009) A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer. Cancer Res 69:6685–6693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moon HJ, Finney J, Ronnebaum T, Mure M (2014) Human lysyl oxidase-like 2. Bioorg Chem 57:231–241

    Article  CAS  PubMed  Google Scholar 

  • Nellaiappan K, Risitano A, Liu G, Nicklas G, Kagan HM (2000) Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. J Cell Biochem 79:576–582

    Article  CAS  PubMed  Google Scholar 

  • Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, Trusk T, Potts JD, Goodwin RL, Davis J, Hoffman S, Wen X, Sugi Y, Kern CB, Mjaatvedt CH, Turner DK, Oka T, Conway SJ, Molkentin JD, Forgacs G, Markwald RR (2007) Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101:695–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ozdener GB, Bais MV, Trackman PC (2016) Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide. Mol Oncol 10:1–23

    Article  CAS  PubMed  Google Scholar 

  • Palamakumbura AH, Jeay S, Guo Y, Pischon N, Sommer P, Sonenshein GE, Trackman PC (2004) The propeptide domain of lysyl oxidase induces phenotypic reversion of ras-transformed cells. J Biol Chem 279:40593–40600

    Article  CAS  PubMed  Google Scholar 

  • Palamakumbura AH, Vora SR, Nugent MA, Kirsch KH, Sonenshein GE, Trackman PC (2009) Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling. Oncogene 28:3390–3400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panchenko MV, Stetler-Stevenson WG, Trubetskoy OV, Gacheru SN, Kagan HM (1996) Metalloproteinase activity secreted by fibrogenic cells in the processing of prolysyl oxidase. Potential role of procollagen C-proteinase. J Biol Chem 271:7113–7119

    Article  CAS  PubMed  Google Scholar 

  • Papke CL, Tsunezumi J, Ringuette LJ, Nagaoka H, Terajima M, Yamashiro Y, Urquhart G, Yamauchi M, Davis EC, Yanagisawa H (2015) Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations. Hum Mol Genet 24:5867–5879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng DH, Ungewiss C, Tong P, Byers LA, Wang J, Canales JR, Villalobos PA, Uraoka N, Mino B, Behrens C, Wistuba II, Han RI, Wanna CA, Fahrenholtz M, Grande-Allen KJ, Creighton CJ, Gibbons DL (2017) ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis. Oncogene 36:1925–1938

    Article  CAS  PubMed  Google Scholar 

  • Ren J, Wu X, He W, Shao J, Cheng B, Huang T (2011) Lysyl oxidase 473 G>A polymorphism and breast cancer susceptibility in Chinese Han population. DNA Cell Biol 30:111–116

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez HM, Vaysberg M, Mikels A, McCauley S, Velayo AC, Garcia C, Smith V (2010) Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor. J Biol Chem 285:20964–20974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rucker RB, Kosonen T, Clegg MS, Mitchell AE, Rucker BR, Uriu-Hare JY, Keen CL (1998) Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr 67:996s–1002s

    Article  CAS  PubMed  Google Scholar 

  • Samatar AA, Poulikakos PI (2014) Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov 13:928–942

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Morgan N, Kirsch KH, Trackman PC, Sonenshein GE (2011) The lysyl oxidase propeptide interacts with the receptor-type protein tyrosine phosphatase kappa and inhibits beta-catenin transcriptional activity in lung cancer cells. Mol Cell Biol 31:3286–3297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki T, Hanisch FG, Deutzmann R, Sakai LY, Sakuma T, Miyamoto T, Yamamoto T, Hannappel E, Chu ML, Lanig H, von der Mark K (2016a) Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa. Matrix Biol 56:132–149

    Article  CAS  PubMed  Google Scholar 

  • Sasaki T, Stoop R, Sakai T, Hess A, Deutzmann R, Schlotzer-Schrehardt U, Chu ML, von der Mark K (2016b) Loss of fibulin-4 results in abnormal collagen fibril assembly in bone, caused by impaired lysyl oxidase processing and collagen cross-linking. Matrix Biol 50:53–66

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Trackman PC, Maki JM, Myllyharju J, Kirsch KH, Sonenshein GE (2011) The Ras signaling inhibitor LOX-PP interacts with Hsp70 and c-Raf to reduce Erk activation and transformed phenotype of breast cancer cells. Mol Cell Biol 31:2683–2695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sato S, Zhao Y, Imai M, Simister PC, Feller SM, Trackman PC, Kirsch KH, Sonenshein GE (2013) Inhibition of CIN85-mediated invasion by a novel SH3 domain binding motif in the Lysyl oxidase Propeptide. PLoS One 8:e77288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sebban S, Davidson B, Reich R (2009) Lysyl oxidase-like 4 is alternatively spliced in an anatomic site-specific manner in tumors involving the serosal cavities. Virchows Arch 454:71–79

    Article  CAS  PubMed  Google Scholar 

  • Sebban S, Golan-Gerstl R, Karni R, Vaksman O, Davidson B, Reich R (2013) Alternatively spliced lysyl oxidase-like 4 isoforms have a pro-metastatic role in cancer. Clin Exp Metastasis 30:103–117

    Article  CAS  PubMed  Google Scholar 

  • Shi W, Yang B, Li X, Sun S, Wang L, Jiao S (2012) The effect of lysyl oxidase polymorphism on susceptibility and prognosis of nonsmall cell lung cancer. Tumour Biol 33:2379–2383

    Article  CAS  PubMed  Google Scholar 

  • Shimazaki M, Nakamura K, Kii I, Kashima T, Amizuka N, Li M, Saito M, Fukuda K, Nishiyama T, Kitajima S, Saga Y, Fukayama M, Sata M, Kudo A (2008) Periostin is essential for cardiac healingafter acute myocardial infarction. J Exp Med 205:295–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tchaparian EH, Uriu-Adams JY, Keen CL, Mitchell AE, Rucker RB (2000) Lysyl oxidase and P-ATPase-7A expression during embryonic development in the rat. Arch Biochem Biophys 379:71–77

    Article  CAS  PubMed  Google Scholar 

  • Thomassin L, Werneck CC, Broekelmann TJ, Gleyzal C, Hornstra IK, Mecham RP, Sommer P (2005) The pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem 280:42848–42855

    Article  CAS  PubMed  Google Scholar 

  • Trackman PC (2016a) Enzymatic and non-enzymatic functions of the lysyl oxidase family in bone. Matrix Biol 52-54:7–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trackman PC (2016b) Lysyl oxidase isoforms and potential therapeutic opportunities for fibrosis and cancer. Expert Opin Ther Targets 20:935–945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trackman PC, Bedell-Hogan D, Tang J, Kagan HM (1992) Post-translational glycosylation and proteolytic processing of a lysyl oxidase precursor. J Biol Chem 267:8666–8671

    CAS  PubMed  Google Scholar 

  • Trask TM, Trask BC, Ritty TM, Abrams WR, Rosenbloom J, Mecham RP (2000) Interaction of tropoelastin with the amino-terminal domains of fibrillin-1 and fibrillin-2 suggests a role for the fibrillins in elastic fiber assembly. J Biol Chem 275:24400–24406

    Article  CAS  PubMed  Google Scholar 

  • Uzel MI, Scott IC, Babakhanlou-Chase H, Palamakumbura AH, Pappano WN, Hong HH, Greenspan DS, Trackman PC (2001) Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures. J Biol Chem 276:22537–22543

    Article  CAS  PubMed  Google Scholar 

  • Vora SR, Guo Y, Stephens DN, Salih E, Vu ED, Kirsch KH, Sonenshein GE, Trackman PC (2010a) Characterization of recombinant lysyl oxidase propeptide. Biochemistry 49:2962–2972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vora SR, Palamakumbura AH, Mitsi M, Guo Y, Pischon N, Nugent MA, Trackman PC (2010b) Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of osteoblasts. J Biol Chem 285:7384–7393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Cong JL, Qu LY, Jiang L, Wang Y (2012) Association between lysyl oxidase G473A polymorphism and ovarian cancer in the Han Chinese population. J Int Med Res 40:917–923

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Shen Y, Cheng G, Bo H, Lin J, Zheng M, Li J, Zhao Y, Li W (2016) Lysyl oxidase gene G473A polymorphism and cigarette smoking in association with a high risk of lung and colorectal cancers in a north Chinese population. Int J Environ Res Public Health, https://doi.org/10.3390/ijerph13070635

  • Wong CC, Tse AP, Huang YP, Zhu YT, Chiu DK, Lai RK, Au SL, Kai AK, Lee JM, Wei LL, Tsang FH, Lo RC, Shi J, Zheng YP, Wong CM, Ng IO (2014) Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 60:1645–1658

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Guo Z, Chang X, Kim MS, Nagpal JK, Liu J, Maki JM, Kivirikko KI, Ethier SP, Trink B, Sidransky D (2007) LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer. Cancer Res 67:4123–4129

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Cai C, Tong D, Hou H (2012) Lysyl oxidase G473A polymorphism is associated with increased risk of ovarian cancer. Genet Test Mol Biomarkers 16:915–919

    Article  CAS  PubMed  Google Scholar 

  • Yoon JH, Park JK, Kang YH, Park YK, Nam SW, Lee JY, Park WS (2011) Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a south Korean population. APMIS 119:762–768

    Article  CAS  PubMed  Google Scholar 

  • Zhao BH, Zhou JH (2012) Decreased expression of elastin, fibulin-5 and lysyl oxidase-like 1 in the uterosacral ligaments of postmenopausal women with pelvic organ prolapse. J Obstet Gynaecol Res 38:925–931

    Article  PubMed  Google Scholar 

  • Zhao Y, Min C, Vora SR, Trackman PC, Sonenshein GE, Kirsch KH (2009) The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. J Biol Chem 284:1385–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The support from the National Institute of Dental and Craniofacial Research grant DE023973 is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Henry M. Goldman School of Dental Medicine, Department of Molecular and Cell Biology, Boston University, 700 Albany Street, W-201, Boston, MA, 02118, USA

    Philip C. Trackman

Authors
  1. Philip C. Trackman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip C. Trackman.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trackman, P.C. Functional importance of lysyl oxidase family propeptide regions. J. Cell Commun. Signal. 12, 45–53 (2018). https://doi.org/10.1007/s12079-017-0424-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-017-0424-4

Keywords

Search

Navigation