Research Interests

For good reason, much of modern cancer research has focused on genes whose products regulate cell growth and survival. However, it is becoming increasingly clear that genes whose products regulate tissue architecture play a critical role in tumour progression. In my laboratory we are determining how the functions of such genes are co-opted during breast and ovarian carcinoma progression.

Breast and ovarian carcinomas both arise in ‘epithelia’. Architecturally, the epithelial tissues affected are made up of tightly linked cells that line ducts (ie. breast) or surfaces (ie. ovary). The links between epithelial cells are initiated and maintained by cell adhesion molecules (ie. cadherins). We have developed specialized, 3-dimensional models that allow us to recapitulate normal epithelial tissue architecture outside the body in a tissue culture dish. We are now modulating the expression and function of cell adhesion molecules in these cultures to determine how architectural disruption allows epithelial cells to break away from the original tumor and begin invading surrounding tissues.

Tumor cell invasion is a prerequisite for metastasis. For invasion to occur, cells that have been released from the original tumor mass must be able to migrate through the extracellular matrix (ECM) which acts as a scaffold between and within tissues. Specialized adhesion molecules that link cells to the ECM (ie. integrins) generate signals within cells that cause them to either remain stationary or become migratory. We are determining the specific molecules that are involved in regulating this migratory switch in breast and ovarian tumor cells.

  1. Snyder KA, Hughes MR, Hedberg B, Brandon J, Hernaez DC, Bergqvist P, Cruz E, Po K, Graves ML, Turvey ME, Nielsen JS, Wilkins JA, McColl SR, Babcook JS, Roskelley CD, McNagny KM. (2015) Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapyBreast Cancer Res (In Press). [IF 5.5].
  2. Freeman SA, Jamouille V, Choi K, Hsu BE, Wong HS, Abraham L, Graves ML, Coombs D, Roskelley CD, Das R, Grinstein S and Gold MR. (2015) Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor. Nature Comm. 6:6168. [IF 11.5].
  1. Austin P, Freeman SA, Gray CA, Vogl AW, Gold MR, Andersen RJ, Roberge M and Roskelley CD*. (2013) The invasion inhibitor sarasinoside A1 reverses mesenchymal tumor transformation in an E-cadherin-independent mannerCancer Res 11:530-40. [IF 4.4].
  2. Zhou L, MacDonald G, Graves M, Mueller C, Roskelley CD*. (2013) Microenvironmental regulation of BRCA1 gene expression by c-Jun and Fra2 in pre-malignant human ovarian surface epithelial cells. Cancer Res 11:272-81. [IF 4.4].
  3. Zimmerman C, Austin P, Khong A, McLeod S, Bean B, Forestieri R, Andersen RJ, Jan E, Roberge M, Roskelley CD*. (2013) The small molecule Genkwanine M induces single mode, mesenchymal tumor motilityCell Research 319:908-17. [IF 3.6].
  4. Towle KM, Chaytor JL, Liu H, Austin P, Roberge M, Roskelley CD, Vederas JC (2013) Synthesis and biological studies of neopetrosiamides as inhibitors of cancer cell invasionOrg Biomol Chem 11:1476-81. [IF 3.5].
  5. Cipollone J, Graves M, Koebel M, Kalloger SE, Poon T, Gilks CB, McNagny KM, Roskelley CD*. (2012) The Anti-Adhesive Mucin Podocalyxin May Help Initiate The Transperitoneal Metastasis Of High Grade Serous Ovarian CarcinomaExp. Metastasis 29:239-52. [IF 3.5].
  6. Lymburner S, McLeod S, Purtzki M, Roskelley CD, Xu Z. (2013) Zinc inhibits magnesium-dependent migration of human breast cancer MDA-MB-231 cells on fibronectinJ Nutr Biochem 24:1034-40. [IF 3.9].
  7. Onishi I, Lin PJ, Numata Y, Austin P, Cipollone J, Roberge M, Roskelley CD, Numata M (2012) Organellar Na+/H+ exhanger NHE7 regulates cell adhesion, invasion and anchorage-dependent growth of breast cancer MDA-MB231 cells. Reports 27:311-317. [IF 2.3].
  8. Freeman SA, Lei V, Dang-Lawson M, Mizuno K, Roskelley CD and Gold MR. (2011) Cofilinmediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation Immunol 187:5887-5900. [IF 5.7].
  9. Morrison C*, Mancini S*, Cipollone J, Kappelhoff R, Roskelley CD, Overall C. (2011) Microarray and proteomic analysis of breast cancer cell and osteoblast co-cultures: the role of osteoblast matrix metalloproteinase (MMP)-13 in bone metastasis. Journal of Biological Chemistry 286:34271-85. [IF 4.7].
  10. Maltby S, Freeman SA, Gold MJ, Baker JH, Minchinton AI, Gold MR, Roskelley CD,McNagny KM. (2011) Opposing roles for CD34 in B16 melanoma tumor growth alter early stage vasculature and late stage immune cell infiltrationPLoS One 6(4):e18160. [IF 4.4].
  11. Lou Y, McDonald PC, Oloumi A, Chia SK, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman DG, Clarke B, Sutherland BW, Waterhouse D, Bally MB, Roskelley CD, Overall CM, Minchinton A, Pacchiano F, Carta F, Scozzafava A, Touisni N, Winum JY, Supuran CT, Dedhar S. (2011) Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX InhibitorsCancer Research 71:3364-3376. [IF 7.5].
  12. Tognon CE, Somasiri AM, Evdokimova VE, Trigo G, Uy EE, Melnyk N, Carboni JM, Gottardis MM, Roskelley CD, Pollak M, Sorensen PH. (2011) ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1-R signaling pathwayCancer Research 71:1060-70. [IF 7.5].
  13. Freeman SA, McLeod SJ, Dukowski J, Austin P, Lee CCY, Millen-Martin B, Kubes P, McCafferty DM, Gold MR, Roskelley CD*. (2010) Preventing the activation or cycling of the Rap1 GTPase alters adhesion and cytoskeletal dynamics and blocks metastatic melanoma cell extravasation into the lungsCancer Research 70:4590-601. [IF 8.23].
  14. Austin P, Heller M, Williams DE, Vogl AM, McIntosh LP, Foster LJ, Andersen RJ, Roberge M, Roskelley CD*. (2010) Release of membrane-bound vesicles and inhibition of tumor cell adhesion by the peptide neopetrosiamide A. PLoS One 5:e10836. [IF 4.41].
  15. Tabrizi AD, Kalloger SE, Köbel M, Cipollone J, Roskelley CD, Mehl E, Gilks CB. (2010) Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases. International Journal of Gynecologic Pathology 29:99-107. [IF 2.1].
  16. Liu H, Boudreau MA, Zheng J, Whittal RM, Austin P, Roskelley CD, Roberge M, Andersen RJ, Vederas JC. (2010) Chemical synthesis and biological activity of the neopetrosiamides and their analogues: revision of disulfide bond connectivity. Journal of the American Chemical Society 132:1486-7. [IF 8.6].
  17. Marcotte R, Zhou L, Kim H, Roskelley CD, Muller WJ. (2009) c-Src associates with ErbB2 through an interaction between catalytic domains and confers enhanced transforming potential. Molecular and Cellular Biology 29:5858-71. [IF 5.2].
  18. Kemmer D, McHardy LM, Hoon S, Reberioux D, Giaver G, Nislow C, Roskelley CD, Roberge M. (2009) Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesisBiomedcentral Microbiology 9:e9.
Further publications can be found here.

Graduate Students:   Marcia McCoy, Jane Cippollone

Research Associates:   Lixin Zhou

Technician:   Pamela Austin

Mammary epithelial cells form spherical, alveolus-like structures in 3-dimensional basement membrane culture. The cells are held together by adherens junctions (E-cadherin, green); there is central lumen (hole) in the center of each structure that is caged by the cytoskeleton (filamentous actin, white); the lumen is sealed by tight junctions (occludin, orange).

Ovarian surface epithelial cells polarize and form bulging cystic structures when they are forced to express the cell adhesion molecule E-cadherin.