Dr. Sendurai Mani
The University of Texas MD Anderson Cancer Center
Department of Molecular Pathology
- The role of epithelial-mesenchymal transition (EMT) and the stem-like cells generated by EMT in cancer invasion and metastasis
- The role of FOXC2 in EMT, stem cells and cancer metastasis
Greater than 80% of all tumors are carcinomas, which are derived in epithelial tissues. During the initial stages of carcinogenesis, the cancer cells are confined to the primary site by the continued expression of epithelial cell-cell adhesion molecules and an intact basal lamina. It is known that, as carcinomas progress, a few cancer cells in the primary tumor reactivate an embryonic program, known as epithelial-mesenchymal transition (EMT). Through EMT, these cells gain the mesenchymal-like traits necessary to escape these confinements and metastasize. Previously, I identified several key embryonic transcription factors, including Twist and FOXC2 that regulate both EMT and breast cancer metastasis. In a more recent study, I discovered that human mammary epithelial cells forced to undergo EMT have many properties of stem cells. These findings suggests that EMT not only generates cancer cells with the ability to disseminate to distant organs but also endows these cells with the stem cell properties that seem necessary for the initiation of secondary tumors following dissemination. Presently, my laboratory is interested in further delineating the role that EMT/CSCs plays during cancer metastasis as well as the role of a number of these EMT-associated transcription factors during cancer metastases. To answer these critical questions, we are using a variety of in vitro and in vivo tumor models as well as tissue-specific, inducible, transgenic mouse models. The main goal of my research laboratory is the facilitation of the development of improved prognostic and therapeutic tools targeting cancer metastasis.
Mani SA,* Guo W,* Liao MJ,*Eaton E, Ayyanan A, Zhou A, Brooks M, Reinhard F, Zhang C, Shipitsin M, Campbell, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 133:704-715. (*Denotes equal first authors) Highlighted in Nature Reviews in Cancer (Nature Reviews Cancer 8, 483 (July 2008) and Cell Stem Cell (Cell Stem Cell. 2008 Jun 5;2 (6):511-2)
Onder T, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA (2008) Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways. Cancer Res. 68: 1-10.
Mani SA,* Yang J,* Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA (2007) FOXC2 plays a key role in metastasis and is associated with aggressive basal-like breast cancers. PNAS 104:10069-10074. (*Denotes equal first authors)
Yang J, Mani SA, Weinberg, RA (2006) Exploring a New Twist in Tumor Metastasis. Cancer Research. 66:1-3.
Yang J,* Mani SA,* Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis. Cell. 117:927–939. (*Denotes equal first authors)