This Project is the second of this Center and is entitled, """"""""Stress Induced Changes in Nuclear Structure and Higher Order DNA Organization"""""""". Bacterial cells have developed a number of mechanisms to allow them to respond quickly to environmental stresses and evolve. The cancer cell has adapted many of these properties and is capable of surviving all forms of currently used treatments. In order to survive, cancer has reactivated the evolutionary process in somatic cells from a wide diversity of genotypic and functional cellular components that comprise the cancer population The hypothesis being tested is that the mechanisms of the stress induced phenotypic changes in cell and chromatin structure that play a critical role in evolution and how these processes are perturbed in the development and control of the therapeutic resistance in cancer. This hypothesis will be evaluated with the following specific aims: 1. to examine the molecular mechanisms of adaptive evolution by which stress induces changes in the re-organization of chromosome domains in prokaryotic and eukaryotic systems;2. to determine the alterations in the actual and functional proteomic composition of nuclear structural elements under stressed conditions;and 3. To examine the effects of stress on cellular motility in prokaryotic and eukaryotic systems. These studies should reveal novel insights into the process by which cancer undergoes punctuated evolution and develops resistant to all therapeutic approaches being utilized.

Public Health Relevance

As pointed out several times in this Center, we have made little progress towards developing effective therapies for many cancer types. The studies outlined in this Project are critical to our understanding of how to get beyond the highly resistant nature of cancer cells by taking advantage of some of their diminished abilities to respond to microenvironmental stresses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143803-05
Application #
8535642
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$287,263
Indirect Cost
Name
Princeton University
Department
Type
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Jung, Younghun; Decker, Ann M; Wang, Jingcheng et al. (2016) Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow. Oncotarget 7:25698-711
Han, Weijing; Chen, Shaohua; Yuan, Wei et al. (2016) Oriented collagen fibers direct tumor cell intravasation. Proc Natl Acad Sci U S A 113:11208-11213
Yumoto, Kenji; Eber, Matthew R; Wang, Jingcheng et al. (2016) Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow. Sci Rep 6:36520
Piotrowski-Daspit, Alexandra S; Tien, Joe; Nelson, Celeste M (2016) Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin. Integr Biol (Camb) 8:319-31
Gascard, Philippe; Tlsty, Thea D (2016) Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev 30:1002-19
Amend, Sarah R; Roy, Sounak; Brown, Joel S et al. (2016) Ecological paradigms to understand the dynamics of metastasis. Cancer Lett 380:237-42
van der Toom, Emma E; Verdone, James E; Pienta, Kenneth J (2016) Disseminated tumor cells and dormancy in prostate cancer metastasis. Curr Opin Biotechnol 40:9-15
Amend, Sarah R; Valkenburg, Kenneth C; Pienta, Kenneth J (2016) Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation. J Vis Exp :
Lee, Eunsohl; Wang, Jingcheng; Yumoto, Kenji et al. (2016) DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis. Neoplasia 18:553-66
Pan, Deng; Roy, Somdutta; Gascard, Philippe et al. (2016) SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73. Cell Signal 28:1923-1932

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