Department of Pathology and Laboratory Medicine
Ph.D., Vanderbilt University, 2002
Postdoctoral, Vanderbilt University, 2003-2008
My laboratory is interested in investigating the functions of stromal fibroblasts in the tumor microenvironment during breast cancer progression. Fibroblasts are a major cellular component of the tumor microenvironment and influence cancer cell behavior directly and indirectly through secretion of soluble factors, including growth regulators and angiogenic factors. While genetic alterations in breast fibroblasts may exert pro-tumorigenic effects, little is known of the cellular and molecular signals that regulate fibroblast functions in the tumor microenvironment.
Studies in my laboratory suggest that fibroblasts may interact with breast cancer cells to regulate cancer cell motility and invasion through chemokine signaling. Chemokines are a family of soluble proteins which signal through seven transmembrane G coupled receptors and regulate immune cell recruitment during inflammatory responses and defenses against foreign pathogens. Studies in our laboratory indicate that CCL2 and CXCL1 chemokine signaling may also regulate fibroblast interactions with other cell types in the microenvironment to promote tumor progression. Using multiple approaches including mouse models of cancer, molecular biology, biochemistry and cell culture systems, we are interested in:
Ultimately, we are interested in understanding the functions of stromal cells in the tumor microenvironment and the impact of the tumor microenvironment on metastatic spread. By identifying and understanding the molecular signals that create a tumor permissive environment, these studies may contribute to identifying new molecular targets for therapy and developing improved methods for diagnosing and treating metastatic breast cancer.
Fang WB, Jokar I, Zou A, Lambert D, Dendukuri P and Cheng N. CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 and p42/44MAPK dependent mechanisms. Journal of Biological Chemistry. 2012. In press.
Fang WB, Jokar I, Chytil A, Moses HL, Abel T, Cheng N. Loss of one Tgfbr2 allele in fibroblasts promotes metastasis in MMTV: polyoma middle T transgenic and transplant mouse models of mammary tumor progression. Clin Exp Metastasis. 2011 Mar 4.
Xu BJ, Yan W, Jovanovic B, An AQ, Cheng N, Aakre ME, Yi Y, Eng J, Link AJ, Moses HL. Quantitative analysis of the secretome of TGF-beta signaling-deficient mammary fibroblasts. Proteomics. 2010 Jul;10(13):2458-70.
Hembruff SL, Jokar I, Yang L, Cheng N. Loss of transforming growth factor-beta signaling in mammary fibroblasts enhances CCL2 secretion to promote mammary tumor progression through macrophage-dependent and -independent mechanisms. Neoplasia. 2010 May;12(5):425-33.
Bierie B, Chung CH, Parker JS, Stover DG, Cheng N, Chytil A, Aakre M, Shyr Y, Moses HL. Abrogation of TGF-beta signaling enhances chemokine production and correlates with prognosis in human breast cancer. J Clin Invest. 2009 Jun;119(6):1571-82. Hembruff SL, Cheng N. Chemokine signaling in cancer: Implications on the tumor microenvironment and therapeutic targeting. Cancer Ther. 2009 Apr 14;7(A):254-267.
Nikki Cheng, Ph.D.