Claudia D. Andl, Ph.D.
Assistant Professor of Surgery
Assistant Professor of Cancer Biology
Vanderbilt University Medical Center
Dept. Surgery, D-4303 MCN 2736
Nashville, TN 37232
Cell adhesion and loss thereof during later stages of cancer resulting in metastasis.
Our research focuses on the cell adhesion molecule, E-cadherin. Cell migration and metastasis are often associated with loss of E-cadherin and reduced E-cadherin expression has been associated with unfavorable patient prognosis. More than 50% of patients diagnosed with esophageal cancer, which we study, have unresectable or metastatic disease at the time of presentation. The role of E-cadherin in maintenance of cell adhesion and preservation of the epithelial phenotype is well known, however, its effect on cell signal transduction is less characterized. We have previously shown that 70% of esophageal squamous cell carcinoma demonstrate the coordinated loss of E-cadherin and TGFb receptor II (TbRII). To model E-cadherin and TbRII loss in vitro, we established organotypic cultures which mimic the tumor microenvironment. These cultures allow the analysis of the cross-talk between epithelial and stromal cells as well as the identifcation of signaling pathways modulated during invasion and metastasis. Based in this model we analyze the Activin signlaing pathway and its role in inducing epithelial cell invasion as wel as activating the surrounding stroma (fibroblasts). We further utilize animal models to study tumor progression in vivo and investigate aspects of crosstalk of the epithelial compartment with the tumor microenvironment. Animals with double knock-out of E-cadherin and TGFb receptor II develop squamous head-and-neck cancer. In vitro and in vivo models are also the basis for projects relating to the role of miRNAs in esophageal cancer.
- Le Bras, GF, Allison, GL, Richards, NF, Ansari, SS, Washington, MK, Andl, CD CD44 upregulation in E-cadherin-negative esophageal cancers results in cell invasion. PLoS One, 6(11), e27063, 2011.
- Andl, CD, McCowan, KM, Allison, GL, Rustgi, AK Cathepsin B is the driving force of esophageal cell invasion in a fibroblast-dependent manner. Neoplasia, 12(6), 485-98, 2010.
- Claudia D. Andl, Kelsey M. McCowan, Gillian L. Allison, Anil K. Rustgi Cathepsin B is the driving force of esophageal cell invasion in a fibroblast-dependent manner. Neoplasia, 12(6), 485-498, 2010.
- Andl, CD, Al Moustafa, AE, Deramaudt, TB, O''Neill, GM Cell adhesion signaling and its impact on tumorigenesis. J Oncol, 2010257809, 2010.
- Andl, CD The Misregulation of Cell Adhesion Components during Tumorigenesis: Overview and Commentary. J Oncol, 20102010.
- Oyama, K, Okawa, T, Nakagawa, H, Takaoka, M, Andl, CD, Kim, SH, Klein-Szanto, A, Diehl, JA, Herlyn, M, El-Deiry, W, Rustgi, AK AKT induces senescence in primary esophageal epithelial cells but is permissive for differentiation as revealed in organotypic culture. Oncogene, 26(16), 2353-64, 2007.
- Lioni, M, Brafford, P, Andl, C, Rustgi, A, El-Deiry, W, Herlyn, M, Smalley, KS Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol, 170(2), 709-21, 2007.
- Takaoka, M, Kim, SH, Okawa, T, Michaylira, CZ, Stairs, DB, Johnstone, CN, Andl, CD, Rhoades, B, Lee, JJ, Klein-Szanto, AJ, El-Deiry, WS, Nakagawa, H IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent mechanisms. Cancer Biol Ther, 6(4), 534-40, 2007.
- Okawa, T, Michaylira, CZ, Kalabis, J, Stairs, DB, Nakagawa, H, Andl, CD, Johnstone, CN, Klein-Szanto, AJ, El-Deiry, WS, Cukierman, E, Herlyn, M, Rustgi, AK The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation. Genes Dev, 21(21), 2788-803, 2007.
- Andl, CD, Fargnoli, BB, Okawa, T, Bowser, M, Takaoka, M, Nakagawa, H, Klein-Szanto, A, Hua, X, Herlyn, M, Rustgi, AK Coordinated functions of E-cadherin and transforming growth factor beta receptor II in vitro and in vivo. Cancer Res, 66(20), 9878-85, 2006.
- Takaoka, M, Smith, CE, Mashiba, MK, Okawa, T, Andl, CD, El-Deiry, WS, Nakagawa, H EGF-mediated regulation of IGFBP-3 determines esophageal epithelial cellular response to IGF-I. Am J Physiol Gastrointest Liver Physiol, 290(2), G404-16, 2006.
- Andl, T, Murchison, EP, Liu, F, Zhang, Y, Yunta-Gonzalez, M, Tobias, JW, Andl, CD, Seykora, JT, Hannon, GJ, Millar, SE The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Curr Biol, 16(10), 1041-9, 2006.
- Bosch, FX, Andl, C, Abel, U, Kartenbeck, J E-cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: a comparison of E-cadherin with desmosomal components. Int J Cancer, 114(5), 779-90, 2005.
- Andl, CD, Rustgi, AK No one-way street: cross-talk between e-cadherin and receptor tyrosine kinase (RTK) signaling: a mechanism to regulate RTK activity. Cancer Biol Ther, 4(1), 28-31, 2005.
- Andl, CD, Mizushima, T, Oyama, K, Bowser, M, Nakagawa, H, Rustgi, AK EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. Am J Physiol Gastrointest Liver Physiol, 287(6), G1227-37, 2004.
- Takaoka, M, Harada, H, Andl, CD, Oyama, K, Naomoto, Y, Dempsey, KL, Klein-Szanto, AJ, El-Deiry, WS, Grimberg, A, Nakagawa, H Epidermal growth factor receptor regulates aberrant expression of insulin-like growth factor-binding protein 3. Cancer Res, 64(21), 7711-23, 2004.
- Takaoka, M, Harada, H, Deramaudt, TB, Oyama, K, Andl, CD, Johnstone, CN, Rhoades, B, Enders, GH, Opitz, OG, Nakagawa, H Ha-Ras(G12V) induces senescence in primary and immortalized human esophageal keratinocytes with p53 dysfunction. Oncogene, 23(40), 6760-8, 2004.
- Andl, CD, Mizushima, T, Nakagawa, H, Oyama, K, Harada, H, Chruma, K, Herlyn, M, Rustgi, AK Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem, 278(3), 1824-30, 2003.
- Harada, H, Nakagawa, H, Oyama, K, Takaoka, M, Andl, CD, Jacobmeier, B, von Werder, A, Enders, GH, Opitz, OG, Rustgi, AK Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation. Mol Cancer Res, 1(10), 729-38, 2003.
- Akis, N, Andl, C, Zhou, D A mixed hemadsorption assay for detection of cell surface binding anti-tumor antibodies in human sera. J Immunol Methods, 261(1-2), 119-27, 2002.
- Andl, CD, Stanley, JR Central role of the plakoglobin-binding domain for desmoglein 3 incorporation into desmosomes. J Invest Dermatol, 117(5), 1068-74, 2001.
- Amagai, M, Matsuyoshi, N, Wang, ZH, Andl, C, Stanley, JR Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1. Nat Med, 6(11), 1275-7, 2000.