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breast cancer • organ-specific metastasis
My research focuses on determining the molecular and cellular mechanisms that are engaged by cancer cells that allow them to grow in these different metastatic microenvironments. The most deadly aspect of breast cancer is the spread or metastasis of cancer cells from the primary tumor to sites throughout the body. When breast cancer cells metastasize, they primarily form metastases in specific organs and tissues, including the bones, lungs, liver and brain. We employ mouse models of breast cancer metastasis to identify and functionally test the role of specific proteins in the metastatic process. My group collaborates with clinicians, surgeons and pathologists to clinically validate targets but also to use clinical material from patients with metastatic cancer to identify novel targets that can be further explored in the pre-clinical animal models established in our lab.
LKB1 is a central regulator of tumor initiation and pro-growth metabolism in ErbB2-mediated breast cancer. Dupuy F, Griss T, Blagih J, Bridon G, Avizonis D, Ling C, Dong Z, Siwak DR, Annis MG, Mills GB, Muller WJ, Siegel PM, Jones RG. Cancer Metab. 2013 Aug 14;1(1):18.
A complex containing LPP and α-actinin mediates TGF&beta-induced migration and invasion of ErbB2-expressing breast cancer cells. Ngan E, Northey JJ, Brown CM, Ursini-Siegel J, Siegel PM. J Cell Sci. 2013 May 1;126(Pt 9):1981-91.
Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes. Tabariès S, Dupuy F, Dong Z, Monast A, Annis MG, Spicer J, Ferri LE, Omeroglu A, Basik M, Amir E, Clemons M, Siegel PM. Mol Cell Biol. 2012 Aug;32(15):2979-91.
CCN3 impairs osteoblast and stimulates osteoclast differentiation to favor breast cancer metastasis to bone. Ouellet V, Tiedemann K, Mourskaia A, Fong JE, Tran-Thanh D, Amir E, Clemons M, Perbal B, Komarova SV, Siegel PM. Am J Pathol. 2011 May;178(5):2377-88.
Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer. Rose AA, Grosset AA, Dong Z, Russo C, Macdonald PA, Bertos NR, St-Pierre Y, Simantov R, Hallett M, Park M, Gaboury L, Siegel PM. Clin Cancer Res. 2010 Apr 1;16(7):2147-56.