Xiang (Shawn) Zhang, Ph.D.
Department of Molecular and Cellular Biology and Lester and Sue Smith Breast Center
Ph.D.: Columbia University, New York City
Postdoctoral training: Memorial Sloan Kettering Cancer Center
The Role of Microenvironment in Breast Cancer Metastasis
Although most solid primary tumors can be surgically removed, metastatic relapses often occur, usually accompanied with resistance to adjuvant therapies. Biologically, metastasis can be simplified as a multi-step process involving local invasion, intravasation, transit in circulation, extravasation, tumor re-initiation and outgrowth in secondary organs. In clinics, the manifestation of metastasis exhibits vast diversity in different types and subtypes of cancers. An important clinical feature of metastasis is the site-tropism, i.e., primary tumors of different types tend to disseminate to distinct range of other organs. For instance, while breast tumors frequently spread to bone, lungs, brain and liver, prostate cancer predominantly metastasizes to bone. Another clinical parameter that greatly varies from tumor to tumor is the kinetics of metastasis: some metastases develop rapidly, whereas the others remain latent for years to decades before outgrowth. Breast cancer is a leading cause of death in women despite well established adjuvant therapies, partly because of the heteogeneity of this disease in their metastasis behaviors. The long-term goals of our laboratory are to delineate biological mechanisms underlying the diverse metastasis behaviors of breast tumors, and to find novel therapeutic opportunities for the cure of metastasis.
Our research of metastasis emphasizes the following aspects:
1) Clinical relevance and implications -- we aim to answer questions that are evident and critical in clinics and to reveal mechanisms that are likely to play roles in human tumors.
2) Stroma as an integral part in tumor progression -- we hypothesize that many metastasis characteristics exhibited by various subtypes of breast cancer are determined by stromal components.
3) Integrative approaches -- we utilize multidisciplinary techniques including methods in molecular biology, cell biology, histology, microscopy, bioinformatics and system biology.
Baylor College of Medicine
One Baylor Plaza, N1110.4
Houston, TX 77030
- Osakarson T, Acharyyl S, Zhang XH-F, Brogi E and Massagué J. (2011) A tenascin-C niche promotes Notch signaling and viability in breast cancer cells that invade the lungs. Nature Medicine 17(7):867-74
- Kim M-Y, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH-F, Norton L and Massagué J. (2009) Mechanisms of tumor self-seeding by circulating cancer cells. Cell 139: 1315-26.
- Nguyen DX, Chiang AC, Zhang XH-F, Kim JY, Kris M, Ladanyi M, Gerald WL and Massagué J. (2009) WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 138: 51-62.
- Zhang* XH-F, Wang* Q, Gerald WL, Hudis C, Norton L, Smid M, Foekens JA and Massagué J. (2009). Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16: 67-78. (* indicates equal first-authorship)
- Bos PD, Zhang XH-F, Nadal C, Shu W, Gomis R, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA and Massagué J . (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005-9.
- Padua D, Zhang XH-F, Wang Q, Nadal C, Gerald WL, Gomis RR and Massagué J . (2008) TGF-beta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133: 66-77.
- Yu Y, Maroney PA, Denker JA, Zhang XH-F, Dybkov O, Lührmann R, Jankowsky E, Chasin LA, and Nilsen TW. (2008) Dynamic Regulation of Alternative Splicing by Silencers that Modulate 5 ' Splice Site Competition. Cell 135 (7): 1224-1236.
- Zhang XH-F and Chasin LA. (2006) Comparison of multiple vertebrate genomes reveals the birth and evolution of human exons Proc Natl Acad Sci U S A 103, 13427-13432
- Zhang XH-F and Chasin LA. (2004) Computational definition of sequence motifs governing the splicing of con=stitutive exons. Genes and Development 18:1241-1250
- Zhang XH-F, Heller KA, Helfer I, Leslie C and Chasin LA. (2003) Sequences Information for the splicing of human pre-mRNA identified by support vector machine classification Genome Research 13: 2637-2650