Polarity proteins regulate mammalian cell-cell junctions and cancer pathogenesis

被引:79
作者
Feigin, Michael E. [1 ]
Muthuswamy, Senthil K. [1 ,2 ]
机构
[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[2] Univ Toronto, Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada
关键词
EPITHELIAL TIGHT JUNCTION; APICO-BASAL POLARITY; ATYPICAL PKC; E-CADHERIN; TGF-BETA; MAMMARY TUMORIGENESIS; DOWN-REGULATION; KINASE-C; COMPLEX; MORPHOGENESIS;
D O I
10.1016/j.ceb.2009.07.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The epithelial cells of multicellular organisms form highly organized tissues specialized for the tasks of protection, secretion, and absorption, all of which require tight regulation of the core processes of cell polarity and tissue architecture. Disruption of these core processes is a critical feature of epithelial tumors. Cell polarity and tissue architecture are intimately linked, as proteins controlling cell shape are also responsible for proper localization and assembly of cell-cell junctions and three-dimensional tissue organization. The extracellular matrix underlying epithelial tissues supports tissue architecture and suppresses malignant growth through regulation of cell adhesion and activation of protective signaling cascades. Emerging evidence is uncovering the mechanisms by which polarity pathways alter the way epithelial cells organize and interact with the tissue microenvironment to promote aberrant growth and invasion during tumorigenesis. We discuss how cell polarity pathways regulate cell-cell junctions and highlight the new insights gained by investigating the role played by polarity pathways during the transformation of epithelial cells.
引用
收藏
页码:694 / 700
页数:7
相关论文
共 57 条
[1]   The transcription factor ZEB1 (δEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity [J].
Aigner, K. ;
Dampier, B. ;
Descovich, L. ;
Mikula, M. ;
Sultan, A. ;
Schreiber, M. ;
Mikulits, W. ;
Brabletz, T. ;
Strand, D. ;
Obrist, P. ;
Sommergruber, W. ;
Schweifer, N. ;
Wernitznig, A. ;
Beug, H. ;
Foisner, R. ;
Eger, A. .
ONCOGENE, 2007, 26 (49) :6979-6988
[2]   Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control [J].
Aranda, Victoria ;
Haire, Teresa ;
Nolan, Marissa E. ;
Calarco, Joseph P. ;
Rosenberg, Avi Z. ;
Fawcett, James P. ;
Pawson, Tony ;
Muthuswamy, Senthil K. .
NATURE CELL BIOLOGY, 2006, 8 (11) :1235-U20
[3]   Hepatocyte growth factor alters the polarity of Madin-Darby canine kidney cell monolayers [J].
Balkovetz, DF ;
Pollack, AL ;
Mostov, KE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (06) :3471-3477
[4]   Crumbs proteins in epithelial morphogenesis [J].
Bazellieres, Elsa ;
Assemat, Emeline ;
Arsanto, Jean-Pierre ;
Le Bivic, Andre ;
Massey-Harroche, Dominique .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2009, 14 :2149-2169
[5]   The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl [J].
Betschinger, J ;
Mechtler, K ;
Knoblich, JA .
NATURE, 2003, 422 (6929) :326-330
[6]   Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly [J].
Chen, XY ;
Macara, IG .
JOURNAL OF CELL BIOLOGY, 2006, 172 (05) :671-678
[7]   Par-3 controls tight junction assembly through the Rac exchange factor Tiam1 [J].
Chen, XY ;
Macara, IG .
NATURE CELL BIOLOGY, 2005, 7 (03) :262-U72
[8]   The role of apoptosis in creating and maintaining luminal space with normal and oncogene-expressing mammary acini [J].
Debnath, J ;
Mills, KR ;
Collins, NL ;
Reginato, MJ ;
Muthuswamy, SK ;
Brugge, JS .
CELL, 2002, 111 (01) :29-40
[9]   Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis [J].
Derksen, Patrick W. B. ;
Liu, Xiaoling ;
Saridin, Francis ;
van der Gulden, Hanneke ;
Zevenhoven, John ;
Evers, Bastiaan ;
van Beijnum, Judy R. ;
Griffioen, Arjan W. ;
Vink, Jacqueline ;
Krimpenfort, Paul ;
Peterse, Johannes L. ;
Cardiff, Robert D. ;
Berns, Anton ;
Jonkers, Jos .
CANCER CELL, 2006, 10 (05) :437-449
[10]   Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling [J].
Dow, L. E. ;
Elsum, I. A. ;
King, C. L. ;
Kinross, K. M. ;
Richardson, H. E. ;
Humbert, P. O. .
ONCOGENE, 2008, 27 (46) :5988-6001