Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pbio.1001199
Title: Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer
Authors: Maxwell C.A.
Benítez J.
Gómez-Baldó L.
Osorio A.
Bonifaci N.
Fernández-Ramires R.
Costes S.V.
Guinó E.
Chen H. 
Evans G.J.R.
Mohan P.
Català I.
Petit A.
Aguilar H.
Villanueva A.
Aytes A.
Serra-Musach J.
Rennert G.
Lejbkowicz F.
Peterlongo P.
Manoukian S.
Peissel B.
Ripamonti C.B.
Bonanni B.
Viel A.
Allavena A.
Bernard L.
Radice P.
Friedman E.
Kaufman B.
Laitman Y.
Dubrovsky M.
Milgrom R.
Jakubowska A.
Cybulski C.
Gorski B.
Jaworska K.
Durda K.
Sukiennicki G.
Lubi?ski J.
Shugart Y.Y.
Domchek S.M.
Letrero R.
Weber B.L.
Hogervorst F.B.L.
Rookus M.A.
Collee J.M.
Devilee P.
Ligtenberg M.J.
van der Luijt R.B.
Aalfs C.M.
Waisfisz Q.
Wijnen J.
van Roozendaal C.E.P.
HEBON Hereditary Breast and Ovarian Cancer Group
EMBRACE Centre for Cancer Genetic Epidemiology
Easton D.F.
Peock S.
Cook M.
Oliver C.
Frost D.
Harrington P.
Lalloo F.
Eeles R.
Izatt L.
Chu C.
Eccles D.
Douglas F.
Brewer C.
Nevanlinna H.
Heikkinen T.
Couch F.J.
Wang X.
Lindor N.M.
Godwin A.K.
Caligo M.A.
Lombardi G.
Loman N.
Karlsson P.
Ehrencrona H.
von Wachenfeldt A.
SWE-BRCA Swedish Breast Cancer Study
Barkardottir R.
Hamann U.
Rashid M.U.
Lasa A.
Caldés T.
Andrés R.
Schmitt M.
Assmann V.
Stevens K.
Offit K.
Curado J.
Tilgner H.
Guigó R.
Aiza G.
Brunet J.
Martrat G.
Urruticoechea A.
Blanco I.
Tihomirova L.
Goldgar D.E.
Buys S.
John E.M.
Miron A.
Southey M.
Daly M.B.
BCFR Breast Cancer Family Registry
Schmutzler R.K.
Wappenschmidt B.
Meindl A.
Arnold N.
Deissler H.
Varon-Mateeva R.
Sutter C.
Niederacher D.
Imyamitov E.
Sinilnikova O.M.
Sinilnikova O.M.
Stoppa-Lyonne D.
Mazoyer S.
Verny-Pierre C.
Castera L.
de Pauw A.
Bignon Y.-J.
Uhrhammer N.
Peyrat J.-P.
Vennin P.
Ferrer S.
Collonge-Rame M.-A.
Mortemousque I.
GEMO Study Collaborators GEMO Study
Spurdle A.B.
Beesley J.
Chen X.
Healey S.
Barcellos-Hoff M.H.
Barcellos-Hoff M.H.
Gruber S.B.
Lázaro C.
Capellá G.
McGuffog L.
Nathanson K.L.
Chenevix-Trench G.
Fleisch M.C.
Moreno V.
Pujana M.A.
Keywords: BRCA1 protein
BRCA2 protein
cell protein
estrogen receptor
nuclear protein
protein AURKA
protein RHAMM
protein TPX2
unclassified drug
aurora kinase
BRCA1 protein
BRCA1 protein, human
BRCA2 protein
BRCA2 protein, human
estrogen receptor
Hermes antigen
hyaluronan mediated motility receptor
hyaluronan-mediated motility receptor
protein serine threonine kinase
scleroprotein
article
breast cancer
breast carcinogenesis
cancer risk
cell polarity
controlled study
epithelial apicobasal polarization
gene locus
gene mutation
genetic analysis
genetic variability
human
human cell
microtubule
molecular interaction
negative feedback
penetrance
protein analysis
protein function
breast
breast tumor
cytology
epithelium cell
female
genetic predisposition
genetics
genotype
HeLa cell
heterozygote
metabolism
pathology
physiology
tumor cell line
tumor suppressor gene
ultrastructure
Antigens, CD44
BRCA1 Protein
BRCA2 Protein
Breast
Breast Neoplasms
Cell Line, Tumor
Cell Polarity
Epithelial Cells
Extracellular Matrix Proteins
Female
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Genetic Variation
Genotype
HeLa Cells
Heterozygote
Humans
Microtubules
Protein-Serine-Threonine Kinases
Receptors, Estrogen
Issue Date: 2011
Citation: Maxwell C.A., Benítez J., Gómez-Baldó L., Osorio A., Bonifaci N., Fernández-Ramires R., Costes S.V., Guinó E., Chen H., Evans G.J.R., Mohan P., Català I., Petit A., Aguilar H., Villanueva A., Aytes A., Serra-Musach J., Rennert G., Lejbkowicz F., Peterlongo P., Manoukian S., Peissel B., Ripamonti C.B., Bonanni B., Viel A., Allavena A., Bernard L., Radice P., Friedman E., Kaufman B., Laitman Y., Dubrovsky M., Milgrom R., Jakubowska A., Cybulski C., Gorski B., Jaworska K., Durda K., Sukiennicki G., Lubi?ski J., Shugart Y.Y., Domchek S.M., Letrero R., Weber B.L., Hogervorst F.B.L., Rookus M.A., Collee J.M., Devilee P., Ligtenberg M.J., van der Luijt R.B., Aalfs C.M., Waisfisz Q., Wijnen J., van Roozendaal C.E.P., HEBON Hereditary Breast and Ovarian Cancer Group, EMBRACE Centre for Cancer Genetic Epidemiology, Easton D.F., Peock S., Cook M., Oliver C., Frost D., Harrington P., Lalloo F., Eeles R., Izatt L., Chu C., Eccles D., Douglas F., Brewer C., Nevanlinna H., Heikkinen T., Couch F.J., Wang X., Lindor N.M., Godwin A.K., Caligo M.A., Lombardi G., Loman N., Karlsson P., Ehrencrona H., von Wachenfeldt A., SWE-BRCA Swedish Breast Cancer Study, Barkardottir R., Hamann U., Rashid M.U., Lasa A., Caldés T., Andrés R., Schmitt M., Assmann V., Stevens K., Offit K., Curado J., Tilgner H., Guigó R., Aiza G., Brunet J., Martrat G., Urruticoechea A., Blanco I., Tihomirova L., Goldgar D.E., Buys S., John E.M., Miron A., Southey M., Daly M.B., BCFR Breast Cancer Family Registry, Schmutzler R.K., Wappenschmidt B., Meindl A., Arnold N., Deissler H., Varon-Mateeva R., Sutter C., Niederacher D., Imyamitov E., Sinilnikova O.M., Sinilnikova O.M., Stoppa-Lyonne D., Mazoyer S., Verny-Pierre C., Castera L., de Pauw A., Bignon Y.-J., Uhrhammer N., Peyrat J.-P., Vennin P., Ferrer S., Collonge-Rame M.-A., Mortemousque I., GEMO Study Collaborators GEMO Study, Spurdle A.B., Beesley J., Chen X., Healey S., Barcellos-Hoff M.H., Barcellos-Hoff M.H., Gruber S.B., Lázaro C., Capellá G., McGuffog L., Nathanson K.L., Chenevix-Trench G., Fleisch M.C., Moreno V., Pujana M.A. (2011). Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. PLoS Biology 9 (11) : e1001199. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.1001199
Abstract: Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02-1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94-1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM. © 2011 Maxwell et al.
Source Title: PLoS Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/161649
ISSN: 15449173
DOI: 10.1371/journal.pbio.1001199
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pbio_1001199.pdf928.54 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

58
checked on May 28, 2020

Page view(s)

59
checked on May 28, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.