Jing Yang Assistant Professor of Pharmacology and Pediatrics Ph.D., Duke University Phone:  (858) 534-1994 Fax:  (858) 534-7390 Email: jingyang@ucsd.edu Lab:  BSB Building, Rm.4065

Key Words: tumor metastasis, Epithelial-Mesenchymal Transition (EMT), Twist, functional genomics, mouse genetics

Tumor metastasis is a complex, multi-step process by which cancer cells spread from a primary site to distant organs and establish secondary tumors.  Although tumor metastasis causes over 90% of cancer deaths, its molecular basis is largely unknown.  The research in my laboratory aims to uncover the genes and the signaling pathways responsible for tumor metastasis.  Our experimental approaches combine molecular biology tools, mouse tumor models, functional genomics and in vivo imaging techniques. 

We have explored a unique mouse breast cancer metastasis model to identify key regulators of tumor metastasis.  Our studies discovered that the Twist transcription factor, a master regulator of early embryonic morphogenesis, is essential for the ability of breast tumor cells to metastasize from the mammary gland to the lung.  We further demonstrated that Twist contributes to tumor invasion and metastasis by activating a latent developmental program termed an epithelial-mesenchymal transition (EMT).  Ectopic expression of Twist resulted in loss of E-cadherin-mediated cell-cell adhesion, activation of mesenchymal markers, and induction of cell motility.  Recently, our and several other studies reported the involvement of Twist and the EMT program in various human malignancies, including breast cancers, gastric cancers, melanomas and neuroblastomas. 

Currently, our research focuses on the following areas:
1) The Molecular Machinery:  Twist, as a key player in tumor metastasis, may exploit several transcription targets to provoke EMT and other aspects of migration and invasion.  We are using genomics, bioinformatics, and biochemical approaches to dissect the signaling and effector pathways that link Twist to EMT and tumor metastasis.  We also plan to test the involvement of these signaling pathways in clinical human cancers.
2) The Dynamic Action:  The in vivo role of EMT in tumor metastasis is still under debated. Clinical observations show that the majority of human carcinoma metastases present an epithelial morphology in distant organs.  We propose that carcinoma cells undergo EMT to invade and disseminate.  Once reaching distant organs, these mesenchymal cells will reverse to an epithelial identity in order to regain proliferating ability. We have established several mouse models to label migrating tumor cells in vivo and to determine how transient activation of Twist and EMT contribute to tumor metastasis.
3) The Inducing Signals:  The ability of carcinoma cells to undergo EMT and metastasize depends on both their genetic/epigenetic alternations and the environmental cues they receive.  Several signaling pathways, including TGF-beta, Wnt, and Notch, are involved in activating cell migration and tissue rearrangement during normal development.  We are very interested in exploring the roles of such signals in inducing Twist, EMT and tumor metastasis.  
4) The Novel Players:  Our previous study identified a number of new candidate genes involved in tumor metastasis.  We will explore their biological functions in tumor metastasis using cell culture models, mouse tumor models, and clinical human tumor samples.

Selected Publications:

Jing Yang*, Sendurai A. Mani*, Joana Liu Donaher, Sridhar Ramaswamy, Raphael A. Itzykson, Christophe Come, Pierre Savagner, Inna Gitelman, Andrea Richardson, Robert A. Weinberg.  (2004).  Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis. Cell 117(7): 927-939.  (*The first two authors contributed equally to this work).

Jing Yang, Sendurai A. Mani, Robert A. Weinberg. (2006) Exploring a New Twist on Tumor Metastasis. Cancer Research, 66 (9): 4549-4552.

Sendurai A. Mani*, Jing Yang*, Mary Brooks, Gunda Schwaninger, Alicia Zhou, Naoyuki Miura, Jeffery L. Kutok, Kimberly Hartwell, Andrea L. Richardson, and Robert A. Weinberg.  (2007) Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers.  Proc. Natl. Acad. Sci. USA.  104(24): 10069-10074.  (*The first two authors contributed equally to this work).

Tamer T. Onder, Piyush B. Gupta, Sandurai A. Mani, Jing Yang, Eric S., Lander, and Robert A. Weinberg. (2008) Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways.  Cancer Research, 68(10): 3645-3654.

Sendurai A. Mani, Wenjun Guo, Mai-Jing Liao, Elinor Ng. Eaton, Ayyakkannu Ayyanan, Alicia Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang, Robert, A. Weinberg.  (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells.  Cell, 133(4): 704-715.

Jing Yang and Robert A. Weinberg.  (2008) Epithelial-Mesenchymal Transition: At the crossroads of development of tumor metastasis.  Developmental Cell, 14(6): 818-829.