Queen's University at Kingston

[ Queen's University Pathology ]

Dr. Xiaolong Yang

Assistant Professor of Pathology and Molecular Medicine

Tel: 613 533-6000x75998
Fax: 613 533-2907
e-mail: yang (at) cliff.path.queensu.ca

Research Laboratory

Molecular and Cellular Biology of Tumor Suppressor Genes

The general research interest of my lab is to understand the molecular and cellular function of tumor suppressors in human cancers using mouse model, human cancer cell lines and clinical tissues. Specifically, the research in my lab is focused on elucidating the roles of two mammalian homologs of Drosophila tumor suppressor gene dLATS (large tumor suppressor), LATS1 and LATS2, in cancer development, cell cycle control, apoptosis and drug response, and cytoskeletal organization. Recently, we have shown that human LATS1 may function as a tumor suppressor as overexpression of LATS1 can suppress human tumor cell growth by either causing G2/M cell cycle arrest or inducing apoptosis (Yang et al., 2001). In addition, we have also demonstrated that human LATS1 binds to LIMK1, a cytoskeletal protein, in vitro and in vivo and inhibits both the phosphorylation of cofilin by LIMK1 and LIMK1-induced cytokinesis defects. Inactivation of LATS1 in cells or gene knockout in mice causes enhanced cytoskeletal actin polymerization, abrogates cytokinesis and increases the percentage of multinucleate cells, which is an important cancer marker (Yang et al., 2004). To further understand the roles of LATS in the development of human cancers, Dr. Yang will screen for mutations of LATS in human cancer patients and further dissect the signal transduction pathways by which LATS control cell cycle, apoptosis, and cytoskeletal organization. Understanding the molecular and cellular function of tumor suppressor genes will be invaluable in developing new targets for the prevention, prognosis, diagnosis, and treatment of cancer.

Selected Publications

  1. Yang X., Yu K., Hao Y., Li D-M., Stewart R., Insogna K. and Xu T. (2004). LATS1 tumor suppressor affects cytokinesis by inhibiting LIMK1. Nature Cell Biol. 6: 609-617.
  2. Ding Z., Green AG, Yang X., Chernenko G, Tang SC. and Pater A. (2002). Retinoic acid inhibits telomerase activity and downregulates expression but does not affect splicing of hTERT: Correlation with cell growth rate inhibition in an vitro cervical carcinogenesis/multidrug-resistance model. Exp. Cell Res. 272: 185-191.
  3. Yang X., Li D-M., Chen W. and Xu T. (2001) Human Homolog of Drosophila lats, LATS1, negatively regulate growth by inducing G2/M arrest or apoptosis. Oncogene 20:6516-6523.
  4. Witcher M., Yang X., Pater A. and Tang S-C. (2001). BAG-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway. Exp. Cell Res. 265: 167-173.
  5. Ding Z., Yang X., Pater A. and Tang S-C. (2000). Resistance to apoptosis is correlated with the reduced caspase-3 activation and enhanced expression of antiapoptotic proteins in human cervical multidrug resistance cells. Biochem. Biophys Res Commun 270: 415-420.
  6. Ding Z., Yang X., Chernenko G. and Tang S.-C. and Pater A. (2000). Human papillomavirus type-16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype. Int. J. Cancer 87: 818-823.
  7. Yang X., Hao Y, Ding Z and Pater A. (2000). BAG-1 promotes apoptosis induced by N (4 hydroxyphenyl)retinamide in human cervical carcinoma cells. Exp. Cell Res. 256:491-499.
  8. Yang X., Hao Y., Pater A. and Tang S-C (2000). Differential expression of anti-apoptotic gene BAG-1 in human breast normal and cancer cell lines and tissues. Clin. Cancer Res. 5: 1816-1822.
  9. Yang X.*, Tang S-C. and Pater A.(1999). Cloning and characterization of human BAG-1 gene promoter: upregulation by tumor-derived p53 mutants. Oncogene 18: 4546-4553. *Corresponding author.
  10. Yang X., Hao Y., Ferenczy, A., Tang S-C. and Pater A. (1999) Overexpression of anti-apoptotic gene BAG-1 in cervical cancer. Exp. Cell Res. 247: 200-207.
  11. Yang X., Chernenko G., Hao Y., Ding Z., Pater M.M., Pater A. and Tang S-T. (1998) Human BAG-1 is generated as four forms by alternative translation initiation and overexpressed in human cancer cells. Oncogene 16: 981-989.
  12. Yang X., Hao Y., Pater M.M., Tang S-T. and Pater A. (1998) Enhanced expression of anti-apoptotic proteins in HPV16-immortalized and CSC-transformed human endocervical cells: correlation with resistance to apoptosis induced by DNA damage. Mol. Carcinog. 22:95-101.
  13. Yang X., Nakao Y., Pater M.M., Tang S-C. and Pater A. (1997) Expression of cellular genes in HPV16-immortalized and cigarette smoke condensate-transformed human endocervical cells. J. Cell. Biochem. 66: 309-321.
  14. Nakao Y., Yang X., Yokoyama M., Ferenczy A., Tang S-C., Pater M.M. and Pater A. (1997) Induction of p16 during immortalization by HPV16 and 18 and not during malignant transformation. Br. J. Cancer 75: 1410-1416.
  15. Nakao Y., Yang X., Yokoyama M., Pater M.M. and Pater A. (1996) Malignant transformation of human ectocervical cells immortalized by HPV18: in vitro model of -carcinogenesis by cigarette smoke. Carcinogenesis 17: 577-583.
  16. Yang X., Nakao Y., Pater M.M. and Pater A. (1996) Identification of two novel cellular genes associated with multistage carcinogenesis of human endocervical cells by mRNA differential display. Carcinogenesis 17: 563-567.
  17. Sarma D., Yang X., Pater M.M. and Pater A. (1996) Resistance to retinoic acid and altered cytokeratin expression of human papillomavirus type 16-immortalized cells after tumorigenesis. Int. J. Cancer 65: 345-350.
  18. Yang X., Jin G., Nakao Y., Rahimtula M., Pater M.M. and Pater A. (1996) Malignant transformation of HPV16-immortalized human endocervical cells by cigarette smoke condensate and characterization of multistage carcinogenesis. Int. J. Cancer 65: 338-344.
  19. Yokoyama M., Nakao Y., Yang X., Sun Q, Pater A. and Pater M.M. (1995) Alterations in physical state and expression of human papillomavirus type 18 DNA following crisis and establishment of immortalized ectocervical cells. Virus Res. 37: 139-151.

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