eBriefing

Out of Line: Cell Polarity in Cancer Progression, Invasion, and Metastasis

Out of Line
Reported by
Alan Dove

Posted September 21, 2009

Overview

Many animal cells are asymmetrical. They have fronts and backs, centers and edges, or tops and bottoms, and they orient many of their structures according to this asymmetry. Cell polarity isn't just involved in normal biology. Indeed, a change in cell polarity is one of the hallmarks of carcinogenesis, and understanding—and stopping—that transition is now one of the hottest topics in cancer research.

At the June 29, 2009, meeting of the Academy's Cancer and Signaling Discussion Group, scientists explored the role of cell polarity in cancer biology. Senthil Muthuswamy explained that tumor formation is a two-step process, with distinct signals causing cells to proliferate and alter their polarity. Enrique Rodriguez-Boulan discussed how epithelial cells use separate mechanisms to sort apical and basolateral proteins. John Condeelis described how macrophages stimulate tumor cells to migrate out of breast tumors, recapitulating breast development, and Ian Macara addressed the role of the Par3 and aPKC genes in mammary stem cell fate.

Use the tabs above to find a meeting report and multimedia from this event.

Articles

Senthil Muthuswamy

Aranda V, Nolan ME, Muthuswamy SK. 2008. Par complex in cancer: a regulator of normal cell polarity joins the dark side. Oncogene 27: 6878-6887.

Muthuswamy SK. 2009. A new tumor suppressor that regulates tissue architecture. PLoS Med. 6: e1000073. Full Text

Zhan L, Rosenberg A, Bergami KC, et al. 2008. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 135: 865-878.

Enrique Rodriguez-Boulan

Deborde S, Perret E, Gravotta D, et al. 2008. Clathrin is a key regulator of basolateral polarity. Nature 452: 719-723.

Salvarezza SB, Deborde S, Schreiner R, et al. 2009. LIM kinase 1 and cofilin regulate actin filament population required for dynamin-dependent apical carrier fission from the trans-Golgi network. Mol. Biol. Cell 20: 438-451. Full Text

Tanos B, Rodriguez-Boulan E. 2008. The epithelial polarity program: machineries involved and their hijacking by cancer. Oncogene 27: 6939-6957.

John Condeelis

Kedrin K, Gligorijevic B, Wyckoff J, et al. 2008. Intravital imaging of metastatic behavior through a mammary imaging window. Nat. Methods 5: 1019-1021.

Philippar U, Roussos ET, Oser M, et al. 2008. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev. Cell 15: 813-828. Full Text

Robinson BD, Sica GL, Liu YF, et al. 2009. Tumor microenvironment of metastasis in human breast carcinoma: a potential prognostic marker linked to hematogenous dissemination. Clin. Cancer Res. 15: 2433-2441.

Ian Macara

Macara IG, Mili S. 2008. Polarity and differential inheritance—universal attributes of life? Cell 135: 801-812.

McCaffrey LM, Macara IG. 2009. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes Dev. 23: 1450-1460.

Mili S, Moissoglu K, Macara IG. 2008. Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature 453: 115-119.

Speakers

Senthil Muthuswamy, PhD

Cold Spring Harbor Laboratory
e-mail | web site | publications

Senthil Muthuswamy received his PhD in biology from McMaster University, Hamilton, Canada and did his postdoctoral fellowship with Joan Brugge at Harvard Medical School. He is currently an associate professor at Cold Spring Harbor Laboratory, NY, and a Professor and Margaret Lau Chair in breast cancer research at Ontario Cancer Institute and University of Toronto, Canada. He has received several research awards: the V Foundation Scholar award, the Rita Allen Scholar award, and the Department of Defense Era of Hope Scholar Award.

Muthuswamy's research goal is to understand how cell polarity pathways regulate epithelial cell morphogenesis, differentiation, and tumorigenesis. Research from his laboratory has demonstrated that alterations in cell polarity pathways cooperate with oncogenes during initiation and progression of tumorigenesis. Since pathologists define cancer on the basis of loss of cell polarity and tissue structure, in addition to increases proliferation rates, understanding how cell polarity regulates initiation and progression of cancer will not only identify biomarkers for precancerous lesions but also identify novel drug targets to prevent progression of precancer to cancer.

Enrique Rodriguez-Boulan, MD

Weill Cornell Medical College
e-mail | web site | publications

Enrique Rodriguez-Boulan received his MD from the University of Buenos Aires. After three years training in Biophysics, he moved to New York University with an International Fogarty Award. At NYU, he trained as a cell biologist and, with his mentor from Argentina, Marcelino Cereijido, co-developed the main tissue culture model to study epithelial polarity, based on the kidney cell line MDCK. He is internationally known for his studies on mechanisms involved in the establishment and maintenance of epithelial polarity. His retinal research deals with the establishment of polarized structure and function in Retinal Pigment Epithelium (RPE) and with retinal diseases (e.g. Age Related Macular Degeneration) that are caused by disruption of RPE's support function for photoreceptors.

John Condeelis, PhD

Albert Einstein College of Medicine
e-mail | web site | publications

John Condeelis is the Judith and Burton P. Resnick Chair in Translational Research, professor and co-chairman of the Department of Anatomy and Structural Biology at the Albert Einstein College of Medicine (AECOM). He is the director of the Cancer Center program "Tumor microenvironment and Metastasis" and co-director, with Robert Singer, of the Gruss Lipper Biophotonics Center of AECOM, a center dedicated to the development and application of optical imaging technologies.

His training is in nuclear physics, optical physics, and cell biology. He worked for the U.S. Navy on particle accelerators and wave guides, and was a PhD student of Robert Allen, the developer of video microscope imaging, with whom he learned live cell microscopy and polarized optics. His current research interest is in tumor cell motility, chemotaxis and invasion during metastasis. He has pioneered the use of combined multiphoton imaging with expression analysis to derive gene expression signatures that define the pathways used by tumor cells in mammary tumors to move and invade blood vessels. He discovered the Invasion Signature of breast tumors. He has devised optical microscopes for uncaging, biosensor detection, and multiphoton imaging for these studies and has used novel caged-enzymes and biosensors to test, in vivo, the predictions of the invasion signature regarding the mechanisms of tumor cell chemotaxis to EGF.

He has authored more than 200 scientific papers on various aspects of cell and cancer biology, and optical imaging. He has held elected office in national societies including President of the New York Society of Experimental Microscopists, 2006–2009 Council of the American Society of Cell Biology, and 2006–2007 Centennial Program Committee of the American Association of Cancer Research.

Ian Macara, PhD

University of Virginia School of Medicine
e-mail | web site | publications

Ian Macara is Harrison Distinguished Professor of Microbiology at the University of Virginia School of Medicine and director of the school's Advanced Microscopy Facility. He is highly regarded for his research in two distinct areas of cell biology: nuclear protein transport and cellular polarity. His research has important implications for understanding the molecular basis for human diseases, including cancer.

Macara received his PhD in biochemistry from the University of Sheffield, England. He then served in various faculty and research positions at top institutions, including the University of Nairobi in Kenya, Harvard University, University of Rochester School of Medicine, and University of Vermont Medical School, before joining the University of Virginia as professor in 1996.


Alan Dove

Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.