Maxwell, Christopher A., Benitez, Javier, Gomez-Baldo, Laia, Osorio, Ana
ORCID: 0000-0001-8124-3984, Bonifaci, Nuria, Fernandez-Ramires, Ricardo, Costes, Sylvain V., Guino, Elisabet
ORCID: 0000-0003-0093-2652, Chen, Helen, Evans, Gareth J. R., Mohan, Pooja, Catala, Isabel, Petit, Anna, Aguilar, Helena, Villanueva, Alberto, Aytes, Alvaro
ORCID: 0000-0003-0725-5340, Serra-Musach, Jordi, Rennert, Gad, Lejbkowicz, Flavio, Peterlongo, Paolo
ORCID: 0000-0001-6951-6855, Manoukian, Siranoush, Peissel, Bernard
ORCID: 0000-0001-9233-3571, Ripamonti, Carla B., Bonanni, Bernardo, Viel, Alessandra
ORCID: 0000-0003-2804-0840, Allavena, Anna, Bernard, Loris, Radice, Paolo
ORCID: 0000-0001-6298-4111, Friedman, Eitan, Kaufman, Bella, Laitman, Yael, Dubrovsky, Maya, Milgrom, Roni, Jakubowska, Anna
ORCID: 0000-0002-5650-0501, Cybulski, Cezary, Gorski, Bohdan, Jaworska, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Lubinski, Jan
ORCID: 0000-0003-2931-3003, Shugart, Yin Yao, Domchek, Susan M., Letrero, Richard, Weber, Barbara L., Hogervorst, Frans B. L., Rookus, Matti A., Collee, J. Margriet, Devilee, Peter, Ligtenberg, Marjolijn J., van der Luijt, Rob B., Aalfs, Cora M., Waisfisz, Quinten, Wijnen, Juul, van Roozendaal, Cornelis E. P., Easton, Douglas F., Peock, Susan, Cook, Margaret, Oliver, Clare, Frost, Debra, Harrington, Patricia, Evans, D. Gareth, Lalloo, Fiona, Eeles, Rosalind
ORCID: 0000-0002-3698-6241, Izatt, Louise, Chu, Carol, Eccles, Diana, Douglas, Fiona, Brewer, Carole, Nevanlinna, Heli
ORCID: 0000-0002-0916-2976, Heikkinen, Tuomas
ORCID: 0000-0003-1154-6204, Couch, Fergus J., Lindor, Noralane M., Wang, Xianshu, Godwin, Andrew K., Caligo, Maria A., Lombardi, Grazia, Loman, Niklas, Karlsson, Per, Ehrencrona, Hans
ORCID: 0000-0002-5589-3622, von Wachenfeldt, Anna, Barkardottir, Rosa Bjork, Hamann, Ute, Rashid, Muhammad U., Lasa, Adriana
ORCID: 0000-0001-9957-9646, Caldes, Trinidad, Andres, Raquel, Schmitt, Michael, Assmann, Volker, Stevens, Kristen, Offit, Kenneth, Curado, Joao
ORCID: 0000-0003-3916-0936, Tilgner, Hagen, Guigo, Roderic, Aiza, Gemma, Brunet, Joan
ORCID: 0000-0003-1945-3512, Castellsague, Joan, Martrat, Griselda, Urruticoechea, Ander
ORCID: 0000-0003-0359-3641, Blanco, Ignacio
ORCID: 0000-0002-7414-7481, Tihomirova, Laima, Goldgar, David E., Buys, Saundra, John, Esther M., Miron, Alexander, Southey, Melissa
ORCID: 0000-0002-6313-9005, Daly, Mary B., Schmutzler, Rita K., Wappenschmidt, Barbara, Meindl, Alfons, Arnold, Norbert
ORCID: 0000-0003-4523-8808, Deissler, Helmut, Varon-Mateeva, Raymonda, Sutter, Christian, Niederacher, Dieter, Imyamitov, Evgeny, Sinilnikova, Olga M., Stoppa-Lyonne, Dominique, Mazoyer, Sylvie
ORCID: 0000-0002-2135-0160, Verny-Pierre, Carole, Castera, Laurent
ORCID: 0000-0002-0459-3400, de Pauw, Antoine, Bignon, Yves-Jean, Uhrhammer, Nancy, Peyrat, Jean-Philippe, Vennin, Philippe, Ferrer, Sandra Fert, Collonge-Rame, Marie-Agnes, Mortemousque, Isabelle, Spurdle, Amanda B., Beesley, Jonathan
ORCID: 0000-0003-1942-325X, Chen, Xiaoqing, Healey, Sue, Barcellos-Hoff, Mary Helen, Vidal, Marc, Gruber, Stephen B., Lazaro, Conxi, Capella, Gabriel
ORCID: 0000-0002-4669-7320, McGuffog, Lesley, Nathanson, Katherine L., Antoniou, Antonis C., Chenevix-Trench, Georgia
ORCID: 0000-0002-1878-2587, Fleisch, Markus C., Moreno, Victor
ORCID: 0000-0002-2818-5487 and Angel Pujana, Miguel
(2011).
Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer.
PLoS. Biol., 9 (11).
SAN FRANCISCO:
PUBLIC LIBRARY SCIENCE.
ISSN 1545-7885
Full text not available from this repository.
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), p(trend) = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94-1.16), p(trend) = 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.
Item Type: |
Journal Article
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Creators: |
Creators | Email | ORCID | ORCID Put Code |
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Maxwell, Christopher A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Benitez, Javier | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Gomez-Baldo, Laia | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Osorio, Ana | UNSPECIFIED | orcid.org/0000-0001-8124-3984 | UNSPECIFIED | Bonifaci, Nuria | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Fernandez-Ramires, Ricardo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Costes, Sylvain V. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Guino, Elisabet | UNSPECIFIED | orcid.org/0000-0003-0093-2652 | UNSPECIFIED | Chen, Helen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Evans, Gareth J. R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Mohan, Pooja | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Catala, Isabel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Petit, Anna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Aguilar, Helena | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Villanueva, Alberto | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Aytes, Alvaro | UNSPECIFIED | orcid.org/0000-0003-0725-5340 | UNSPECIFIED | Serra-Musach, Jordi | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Rennert, Gad | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lejbkowicz, Flavio | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Peterlongo, Paolo | UNSPECIFIED | orcid.org/0000-0001-6951-6855 | UNSPECIFIED | Manoukian, Siranoush | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Peissel, Bernard | UNSPECIFIED | orcid.org/0000-0001-9233-3571 | UNSPECIFIED | Ripamonti, Carla B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bonanni, Bernardo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Viel, Alessandra | UNSPECIFIED | orcid.org/0000-0003-2804-0840 | UNSPECIFIED | Allavena, Anna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bernard, Loris | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Radice, Paolo | UNSPECIFIED | orcid.org/0000-0001-6298-4111 | UNSPECIFIED | Friedman, Eitan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kaufman, Bella | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Laitman, Yael | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dubrovsky, Maya | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Milgrom, Roni | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Jakubowska, Anna | UNSPECIFIED | orcid.org/0000-0002-5650-0501 | UNSPECIFIED | Cybulski, Cezary | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Gorski, Bohdan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Jaworska, Katarzyna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Durda, Katarzyna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Sukiennicki, Grzegorz | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lubinski, Jan | UNSPECIFIED | orcid.org/0000-0003-2931-3003 | UNSPECIFIED | Shugart, Yin Yao | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Domchek, Susan M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Letrero, Richard | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Weber, Barbara L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hogervorst, Frans B. L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Rookus, Matti A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Collee, J. Margriet | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Devilee, Peter | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ligtenberg, Marjolijn J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van der Luijt, Rob B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Aalfs, Cora M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Waisfisz, Quinten | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wijnen, Juul | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van Roozendaal, Cornelis E. P. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Easton, Douglas F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Peock, Susan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Cook, Margaret | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Oliver, Clare | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Frost, Debra | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Harrington, Patricia | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Evans, D. Gareth | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lalloo, Fiona | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Eeles, Rosalind | UNSPECIFIED | orcid.org/0000-0002-3698-6241 | UNSPECIFIED | Izatt, Louise | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chu, Carol | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Eccles, Diana | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Douglas, Fiona | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Brewer, Carole | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Nevanlinna, Heli | UNSPECIFIED | orcid.org/0000-0002-0916-2976 | UNSPECIFIED | Heikkinen, Tuomas | UNSPECIFIED | orcid.org/0000-0003-1154-6204 | UNSPECIFIED | Couch, Fergus J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lindor, Noralane M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang, Xianshu | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Godwin, Andrew K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Caligo, Maria A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lombardi, Grazia | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Loman, Niklas | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Karlsson, Per | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ehrencrona, Hans | UNSPECIFIED | orcid.org/0000-0002-5589-3622 | UNSPECIFIED | von Wachenfeldt, Anna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Barkardottir, Rosa Bjork | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hamann, Ute | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Rashid, Muhammad U. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lasa, Adriana | UNSPECIFIED | orcid.org/0000-0001-9957-9646 | UNSPECIFIED | Caldes, Trinidad | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Andres, Raquel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Schmitt, Michael | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Assmann, Volker | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Stevens, Kristen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Offit, Kenneth | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Curado, Joao | UNSPECIFIED | orcid.org/0000-0003-3916-0936 | UNSPECIFIED | Tilgner, Hagen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Guigo, Roderic | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Aiza, Gemma | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Brunet, Joan | UNSPECIFIED | orcid.org/0000-0003-1945-3512 | UNSPECIFIED | Castellsague, Joan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Martrat, Griselda | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Urruticoechea, Ander | UNSPECIFIED | orcid.org/0000-0003-0359-3641 | UNSPECIFIED | Blanco, Ignacio | UNSPECIFIED | orcid.org/0000-0002-7414-7481 | UNSPECIFIED | Tihomirova, Laima | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Goldgar, David E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Buys, Saundra | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | John, Esther M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Miron, Alexander | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Southey, Melissa | UNSPECIFIED | orcid.org/0000-0002-6313-9005 | UNSPECIFIED | Daly, Mary B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Schmutzler, Rita K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wappenschmidt, Barbara | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Meindl, Alfons | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Arnold, Norbert | UNSPECIFIED | orcid.org/0000-0003-4523-8808 | UNSPECIFIED | Deissler, Helmut | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Varon-Mateeva, Raymonda | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Sutter, Christian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Niederacher, Dieter | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Imyamitov, Evgeny | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Sinilnikova, Olga M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Stoppa-Lyonne, Dominique | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Mazoyer, Sylvie | UNSPECIFIED | orcid.org/0000-0002-2135-0160 | UNSPECIFIED | Verny-Pierre, Carole | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Castera, Laurent | UNSPECIFIED | orcid.org/0000-0002-0459-3400 | UNSPECIFIED | de Pauw, Antoine | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bignon, Yves-Jean | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Uhrhammer, Nancy | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Peyrat, Jean-Philippe | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Vennin, Philippe | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ferrer, Sandra Fert | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Collonge-Rame, Marie-Agnes | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Mortemousque, Isabelle | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Spurdle, Amanda B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Beesley, Jonathan | UNSPECIFIED | orcid.org/0000-0003-1942-325X | UNSPECIFIED | Chen, Xiaoqing | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Healey, Sue | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Barcellos-Hoff, Mary Helen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Vidal, Marc | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Gruber, Stephen B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lazaro, Conxi | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Capella, Gabriel | UNSPECIFIED | orcid.org/0000-0002-4669-7320 | UNSPECIFIED | McGuffog, Lesley | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Nathanson, Katherine L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Antoniou, Antonis C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chenevix-Trench, Georgia | UNSPECIFIED | orcid.org/0000-0002-1878-2587 | UNSPECIFIED | Fleisch, Markus C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Moreno, Victor | UNSPECIFIED | orcid.org/0000-0002-2818-5487 | UNSPECIFIED | Angel Pujana, Miguel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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URN: |
urn:nbn:de:hbz:38-486808 |
DOI: |
10.1371/journal.pbio.1001199 |
Journal or Publication Title: |
PLoS. Biol. |
Volume: |
9 |
Number: |
11 |
Date: |
2011 |
Publisher: |
PUBLIC LIBRARY SCIENCE |
Place of Publication: |
SAN FRANCISCO |
ISSN: |
1545-7885 |
Language: |
English |
Faculty: |
Unspecified |
Divisions: |
Unspecified |
Subjects: |
no entry |
Uncontrolled Keywords: |
Keywords | Language |
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CENTROSOMAL MICROTUBULE NUCLEATION; PROGENITOR-CELL FATE; MUTATION CARRIERS; MAMMARY-GLAND; MITOTIC SPINDLE; STEM-CELLS; MULTIPLE-MYELOMA; BRCA1-DEPENDENT UBIQUITINATION; EXPRESSION SIGNATURE; ADHERENS JUNCTIONS | Multiple languages | Biochemistry & Molecular Biology; Biology | Multiple languages |
|
URI: |
http://kups.ub.uni-koeln.de/id/eprint/48680 |
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