Metastatic progression of the primary tumor accounts for the majority of cancer deaths. While the initial steps of the metastatic cascade are rather well defined, identification of targets to block this process remains a major clinical challenge. Previous studies have elegantly investigated the mechanistic contribution of tumor cell intrinsic properties that promote metastasis in bladder urothelial carcinomas. However, the functional significance of the tumor microenvironment and its contribution to this complicated process is not well characterized, and therefore, warrants investigation. The long-term goal of this renewal application is to continue explore how collagens?a major extracellular matrix component of the microenvironment?act as a ligand to mediate crosstalk with their receptor on tumor cells to facilitate the metastatic cascade. We will investigate the downstream regulatory mechanisms of collagen receptor signaling in both the primary tumor and metastatic sites, and to exploit these regulatory processes as a revolutionizing approach to target metastases. Such innovative approaches to perturb collagen-cancer crosstalk?not only at the primary tumor but also at the metastatic niche?will move the field forward by providing a new conception in metastatic disease management, and likely extend beyond bladder carcinomas to other cancer types.

Public Health Relevance

Metastatic bladder cancer is a devastating disease with a 5-year survival rate of only 5.4%. While the initial steps of the metastatic cascade are rather well defined, identification of targets to block this process continues to be a major clinical challenge. Discovering the regulatory mechanisms by which the metastatic microenvironment support tumor cell colonization and survival will enable design of new strategies not only targeting the primary tumors, but also eradicating metastatic foci ? a potential new breakthrough.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Snyderwine, Elizabeth G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cedars-Sinai Medical Center
Los Angeles
United States
Zip Code
Mo, Qianxing; Nikolos, Fotis; Chen, Fengju et al. (2018) Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas. J Natl Cancer Inst 110:448-459
Mo, Qianxing; Shen, Ronglai; Guo, Cui et al. (2018) A fully Bayesian latent variable model for integrative clustering analysis of multi-type omics data. Biostatistics 19:71-86
Rodriguez-Brenes, Ignacio A; Kurtova, Antonina V; Lin, Christopher et al. (2017) Cellular Hierarchy as a Determinant of Tumor Sensitivity to Chemotherapy. Cancer Res 77:2231-2241
Brooks, Michael; Mo, Qianxing; Krasnow, Ross et al. (2016) Positive association of collagen type I with non-muscle invasive bladder cancer progression. Oncotarget 7:82609-82619
Chan, Keith Syson (2016) Molecular Pathways: Targeting Cancer Stem Cells Awakened by Chemotherapy to Abrogate Tumor Repopulation. Clin Cancer Res 22:802-6
Kurtova, Antonina V; Xiao, Jing; Mo, Qianxing et al. (2015) Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 517:209-13
Kim, Woosook; Barron, David A; San Martin, Rebeca et al. (2014) RUNX1 is essential for mesenchymal stem cell proliferation and myofibroblast differentiation. Proc Natl Acad Sci U S A 111:16389-94