Life Sciences & Biotechnology
Title : | Deciphering the tumor-associated functions of pregnancy zone protein in breast cancer |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. syed Khizer Hasan, Tata Memorial Centre (Hospital), Maharashtra |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | shasan@actrec.gov.in |
Details
Executive Summary : | Pregnancy zone protein (PZP) is crucial for maintaining the immune-tolerant status of a fetus during pregnancy and has been linked to a reduced risk of developing breast cancer later in life. Genetic ablation of PZP has been shown to inhibit tamoxifen-induced apoptosis and enhance cell proliferation, migration, and colony-forming capacity in breast cancer cells. PZP is abundant in human plasma during pregnancy and found in the extracellular matrix (ECM) of tissue. In vitro, PZP binds with transforming growth factors (TGF-β1/β2), but the biological significance and precise mechanism of this interaction remain to be determined. The TGF-β1 ligand, also known as latent TGF-β, is accumulated in the ECM as an inactive pro-peptide. The activation of latent TGF-β by secretory proteins of ECM is context-dependent, and the biology of vast amounts of latent TGF-β ligand in ECM is enigmatic. The hypothesis is that PZP as an antagonist interacts with TGF-β ligand to regulate downstream TGF-β/sMAD signaling. If PZP levels are low, TGF-β ligand gets upregulated, potentially becoming a prometastatic inducer inducing epithelial-mesenchymal transition (EMT), invasion, survival, and angiogenesis. This project proposes that PZP plays an indispensable role in breast cancer progression via the PZP/TGF-β/sMAD axis, which could be a potential therapeutic target of TGF-β inhibitors. The aim is to identify and characterize interacting partners of PZP and elucidate the molecular mechanisms underlying PZP-mediated regulation of TGF-β/sMAD signaling and its role in tumor progression using syngeneic mouse models of breast cancer with genetically manipulated PZP. |
Co-PI: | Dr. sudeep Gupta, Tata Memorial Centre (Hospital), Mumbai, Maharashtra400012 |
Total Budget (INR): | 70,77,610 |
Organizations involved