Novel molecules regulating cAMP signaling and their implications in Nanomedicine Based Therapy for Breast Cancer Associated Metastasis | Shiv Nadar University
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Novel molecules regulating cAMP signaling and their implications in Nanomedicine Based Therapy for Breast Cancer Associated Metastasis

Breast cancer is one of the leading cause of death among women. Mainly three different types of breast cancer have been identified: Ductal Carcinoma in situ, Invasive Ductal Carcinoma and Triple Negative Breast Cancer (TNBC). TNBC is most aggressive form of cancer and there is no effective therapy available due to lack of Estrogen, Progesterone and HER2 receptor (ER-, PR- and HER2). Cyclic Adenosine monophosphate (cAMP) is one of the key secondary messenger which is involved in several physiological processes such as cell-cell interaction, migration and secretion. It usually acts as downstream signaling molecule for G-Protein Coupled Receptors (GPCRs). cAMP activates the downstream molecule through two signaling pathway: PKA-dependent and PKA-independent pathway. PKA-independent pathway is driven by Exchange Factor Directly Activated by cAMP (EPAC) which further activates the RAP1 and RAP2 protein. There are two isoforms of EPAC: EPAC1 and EPAC2. Both proteins activate RAP1 and RAP2. EPAC1 which is also known as RAPGEF3 is found to be involved in actin remodeling, apoptosis, cancer cell invasion and angiogenesis. EPAC1 interacts with several molecules such as AKT1, CREB and SOCS3 proteins. It also acts as a scaffold protein. EPAC1 protein is dysregulated in different types of cancer which associates with cancer cell progression and survival. Role of EPAC1 in breast cancer has not been explored extensively. Here, in this study we have explored the role of EPAC1 in breast cancer and shown its role in tumor progression. We have shown that EPAC1 participates in tumor induced angiogenesis and allow cells to migrate and invade. Further to explore its therapeutic and translational potential, we have used the novel graphene and PAMAM based nanoparticle (GPD) and delivered the EPAC1 siRNA in breast cancer cells. We showed the downregulation of EPAC1  gene expression through graphene based nanoparticles and its further effect on cancer metastasis properties.

Department: 
Life Sciences
Year: 
2018
Student Name: 
Naveen Kumar

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