Abstract
Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. We are in a great to need identify novel membrane proteins associated with migration and metastasis of breast cancer cells. CD271, a single transmembrane protein belongs to tumor necrosis factor receptor family acts and play its role in proliferation of cancer cell. The purpose of this study is to investigate the role of CD271 in breast cancer. In this study we analyzed the mRNA expression of CD271 in breast tumor tissue, breast cancer cell line MCF7 and isolated cancer stem cells (MCF7-CSCs) by RT-qPCR. We also measured the protein levels through western blotting in MCF-7 cell line. CD271 was upregulated in breast cancer patients among all age groups. Within the promoter region of CD271, there is a binding site for NF-κB1 which overlaps a putative quadraplex forming sequence. While CD271 also activates NF-κB pathway, down regulation of CD271 through quadraplex targeting resulted in inhibition of NF-κB and its downstream targets Nanog and Sox2. In conclusion, our data shows that CD271 and NF-κB are regulated in interdependent manner. Upon CD271 inhibition, the NF-κB expression also reduces which in turn affects the cell proliferation and migration. These results suggest that CD271 is playing a crucial rule in cancer progression by regulating NF-κB and is a good candidate for the therapeutic targeting.
Highlights
Breast cancer is the serious health issue and 2nd leading cause of mortality among all other cancer accounting for 11.7% of cases worldwide[1, 2] .Breast tumors are known to be composed of diverse group of cells including cancer stem cells (CSCs).CSCs have an ability to control the tumorigenicity and resist conventional therapies
In this study we analyzed the expression of CD271 in breast tumor tissue, breast cancer cell line MCF7 and isolated cancer stem cells (MCF7-CSCs) by quantitative real-time polymerase chain reaction (RTqPCR)
Upon CD271 inhibition, the NF-κB expression reduces which effected the cell proliferation and migration. These results suggest that NF-κB is regulated by CD271 is playing a crucial role in cancer development and could be a potential therapeutic target
Summary
Breast cancer is the serious health issue and 2nd leading cause of mortality among all other cancer accounting for 11.7% of cases worldwide[1, 2] .Breast tumors are known to be composed of diverse group of cells including cancer stem cells (CSCs).CSCs have an ability to control the tumorigenicity and resist conventional therapies. CD271, known as nerve growth factor receptor (NGFR) is a transmembrane protein It belongs to the tumor necrosis factor receptor (TNFR) superfamily [5] and plays a pivotal role in development and regeneration of sympathetic and sensory nervous system [6].It performs a dual role by acting as an antiproliferative agent which control cell apoptosis by the facilitation of cytochrome C release from mitochondria and activation of Caspases 9, 6 and 3. It has been involved in cell proliferation and promote invasiveness by MAPK and (PI3K)/ AKT signaling pathway[7,8,9,10]. The purpose of this study is to investigate the role of CD271 in breast cancer
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