Jitesh Pratap, PhD, is an associate professor in the Department of Anatomy & Cell Biology. Pratap received his PhD degree from Panjab University, India. He completed his postdoctoral studies at the University of Massachusetts Medical School where he began his studies of metastatic breast cancer and showed that nuclear protein Runx2 promotes cancer-related properties.
Metastasis is a step in advanced cancer development that is lethal as cancer cells often spread to bone. The current understanding of the regulatory mechanisms of bone metastasis is still not clear. Metastasis to bone is associated with osteoclast and osteoblast recruitment, resulting in the liberation of growth factors from the bone matrix, which can feed back to enhance tumor growth resulting in the “vicious cycle” of bone metastases.
We are investigating cellular and molecular events during bone and cancer cell interactions that influence cancer cell survival during metastases. We combine genetics, molecular, biochemical and cell biological approaches to address two aspects of bone metastasis:
Growth factor signaling
Our focus is to understand the survival mechanisms of metastatic cancer cells in the bone microenvironment. In the bone microenvironment, metastasized cancer cells activate signaling pathways for growth factors. The paracrine signaling (e.g., IGF, TGFβ, PTHrP and ET-1) interplay between tumor cells and the bone leads to a selective growth advantage for the tumor cells.
We are particularly interested in regulatory network of insulin-like growth factor-1 receptor (IGF-1R). Bone is the second richest source of IGF-I, and its binding to the IGF-1R on cancer cells leads to receptor auto-phosphorylation and activation of at least two pro-survival signaling pathways: phosphoinositol 3-kinase (PI3K)-Akt signaling and extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK).
We identified, in bone-derived populations of metastatic breast cancer cells, a novel regulatory axis for IGF-1R via the Runt-related master transcription factor (Runx2). Our current studies center on crosstalk between Runx2 and growth factor signaling in metastatic cancer cells. We use a variety of cutting-edge cellular and molecular approaches and involve state-of-the-art live animal bio-imaging and cell imaging to address our biological questions.
Cancer cell metabolism
The unique biochemical (e.g., growth factors, nutrients) and physical (e.g., acidic pH) characteristics of the bone niche provide homing signals to the cancer cells. Cancer cells have high energetic and anabolic needs and are known to adapt their metabolism by activating distinct nutrient metabolic pathways to be able to survive and keep proliferating under conditions of nutrient stress. We are examining the mechanisms of metabolic stress response by which metastatic cancer cells survive in the bone microenvironment.
Jitesh Pratap, PhD’s grants
Metavivor Foundation (PI): “Novel Regulatory Mechanisms of Cell Survival During Bone Metastasis of Breast Cancer”
American Society of Bone and Mineral Research (PI): “Regulation of Runx2 in Bone Metastasis”
Tandon M, Chen Z, Othman AH, Pratap J. “Role of Runx2 in IGF-1Rβ/Akt- and AMPK/Erk-Dependent Growth, Survival and Sensitivity Towards Metformin in Breast Cancer Bone Metastasis.” Oncogene. 2016 Jan 25. doi: 10.1038/onc.2015.
Wu Q, Madany P, Akech J, Dobson JR, Douthwright S, Browne G, Colby JL, Winter GE, Bradner JE, Pratap J, Sluder G, Bhargava R, Chiosea SI, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Nickerson JA, Imbalzano AN. “The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation.” J Cell Physiol. 2015; 230 (11):2683-94.
Tandon M, Chen Z, Pratap J. “Role of Runx2 in Crosstalk Between Mek/Erk and PI3K/Akt Signaling in MCF-10A Cells.” J Cell Biochem. 2014; 115(12): 2208-17.
Dobson JR, Taipaleenmäki H, Hu YJ, Hong D, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Pratap J. “hsa-mir-30c Promotes the Invasive Phenotype of Metastatic Breast Cancer Cells by Targeting NOV/CCN3.” Cancer Cell Int. 2014; 14:73.
Tandon M, Chen Z, Pratap J. “Runx2 Activates PI3K/Akt Signaling via mTORC2 Regulation in Invasive Breast Cancer Cells.” Breast Cancer Res. 2014;16 (1):R16.
Dutta A, Li J, Lu H, Akech J, Pratap J, Wang T, Zerlanko BJ, FitzGerald TJ, Jiang Z, Birbe R, Wixted J, Violette SM, Stein JL, Stein GS, Lian JB, Languino LR. “Integrin αvβ6 Promotes an Osteolytic Program in Cancer Cells by Upregulating MMP2.” Cancer Res. 2014; 74(5):1598-608.
Tandon M, Gokul K, Ali SA, Chen Z, Lian J, Stein GS, Pratap J. “Runx2 Mediates Epigenetic Silencing of the Bone Morphogenetic Protein-3B (BMP-3B/GDF10) in Lung Cancer Cells.” Mol Cancer. 2012; 11: 27.
Eapen A, Ramachandran A, Pratap J, George A. “Activation of the ERK1/2 Mitogen-Activated Protein Kinase Cascade by Dentin Matrix Protein 1 Promotes Osteoblast Differentiation. Cells Tissues Organs. 2011; 194(2-4):255-60.
Pratap J, Akech J, Wixted JJ, Szabo G, Hussain S, McGee-Lawrence ME, Li X, Bedard K, Dhillon RJ, van Wijnen AJ, Stein JL, Stein GS, Westendorf JJ, Lian JB. “The Histone Deacetylase Inhibitor, Vorinostat, Reduces Tumor Growth at the Metastatic Bone Site and Associated Osteolysis, but Promotes Normal Bone Loss.” Mol Cancer Ther. 2010 (12): 3210-20.
Leong DT, Lim J, Goh X, Pratap J, Pereira BP, Kwok HS, Nathan SS, Dobson JR, Lian JB, Ito Y, Voorhoeve PM, Stein GS, Salto-Tellez M, Cool SM, van Wijnen AJ. “Cancer-Related Ectopic Expression of the Bone-Related Transcription Factor RUNX2 in Non-Osseous Metastatic Tumor Cells Is Linked to Cell Proliferation and Motility.” Breast Cancer Res. 2010; 12(5):R89.
Pratap J, Lian JB, Stein GS. “Metastatic Bone Disease: Role of Transcription Factors and Future Targets.” Bone. 2011; 48(1):30-6.
Akech J, Wixted JJ, Bedard K, van der Deen M, Hussain S, Guise TA, van Wijnen AJ, Stein JL, Languino LR, Altieri DC, Pratap J, Keller E, Stein GS, Lian JB. “Runx2 Association with Progression of Prostate Cancer in Patients: Mechanisms Mediating Bone Osteolysis and Osteoblastic Metastatic Lesions. Oncogene. 2010, 29(6):811-21.
Pratap J, Imbalzano KM, Underwood JM, Cohet N, Gokul K, Akech J, van Wijnen AJ, Stein JL, Imbalzano AN, Nickerson JA, Lian JB, Stein GS. “Ectopic Runx2 Expression in Mammary Epithelial Cells Disrupts Formation of Normal Acini Structure: Implications for Breast Cancer Progression.” Cancer Res. 2009; 69(17):6807-14.
Complete list of published work
A complete listing of Pratap’s published work can be found on PubMed.
Jitesh Pratap, PhD
Department of Anatomy & Cell Biology
1750 W. Harrison St., Room 1409B
Chicago, IL 60612
Phone: (312) 563-4633