Date of Award

12-14-2015

Document Type

Open Access Thesis

Department

Chemistry and Biochemistry

First Advisor

Mythreye Karthikeyan

Abstract

Cancer cells can be viewed as such cells, which have disrupted/aberrant signaling pathways for maintaining cellular homoeostasis. Identifying such altered signaling mechanisms can help us target these pathways in a better way. GDF-2 (Growth and differentiation factor – 2) or BMP9 (Bone morphogenetic protein – 9), a multifunctional cytokine, is a member of the Bone Morphogenetic Protein subfamily, under TGFβ superfamily, with roles distinct from BMP2/4/7. While GDF-2 is known to be one of the most potent ectopic inducers of bone and cartilage formation, it rose to significance with the identification of its receptor ALK1 in endothelial cells. TGFβ’s role in cancer progression could be described as both agonistic and antagonistic. It maintains tissue homeostasis and prevents incipient tumors from progressing down the path to malignancy. But cancer cells have the capacity to avoid the suppressive influence of TGFβ pathway. Pathological forms of TGFβ signaling promote tumor growth and invasion, evasion of immune surveillance and cancer cell metastasis. Apart from the Cterminal phosphorylation of smad2/3 by TGFβ, it can also phosphorylate the linker region. We find that GDF-2 can regulate smad phosphorylation by phosphorylating smad1/5 at the C-terminus to regulate cell survival [1-5]. Interestingly, GDF2 can also mediate linker phosphorylation of smad2 and not smad1 in a subset of epithelial cancer and non-cancerous cells. My Studies indicate that GDF-2 mediated linker smad2 phosphorylation can antagonize TGFβ signaling implicating that the balance in the level of growth factors is an important factor in mediating downstream signaling pathways

Rights

© 2015, Tirthankar Bandyopadhyay

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