Stability and thermodynamic investigation of embryonic stem cell marker Sox2 in breast cancer stem cellsby spectroscopic and modeling techniques

Sox2 (sex-determining region Y-box protein 2) is a transcription factor involved in the regulation of embryonic development and determination of cell fate. Sox2 is essential for self-renewal and pluripotency of embryonic stem cells (ESCs), as gene knockdown of Sox2 induces differentiation in ESCs. Sox2 is aberrantly expressed in breast and other cancers. In breast cancers, 16–30% of the tumors have been reported to express Sox2 detectable by immunohistochemistry while adult benign breast tissues show low to no Sox2 expression. Sox2 expression has been reported in all 4 majormolecular subtypes of breast cancer. In addition, Sox2 immunoreactivity correlates with a worse clinical outcome in breast cancer patients. Sox2 siRNA treatment has been shown to decrease proliferation in breast cancer cells, and Sox2 overexpression has been reported to increase in mammosphere formation in vitro. Sox2 expression was associated with larger tumor size and positive lymph node status. Cancer stem cells (CSCs), are responsible for tumor relapse, metastasis, and chemoresistance. Present chemotherapy modalities eliminate the bulk of tumor cells, but cannot eliminate the core of these cancer stem cells. Therefore, focusing therapies on cancer stem cells is more effective for the treatment of breast cancer. The conformational stability of a protein is defined as the free energy change (ΔGo). The marginal stability of proteins makes the use of certain proteins in industrial or pharmaceutical applications difficult, especially when the protein is subjected to extremes of temperature and pH, or to destabilizing solvents such as organic solvents. The aim of this study was to investigation stability Sox2‚ Under different environmental conditions (such as pH‚ polarization‚ surfactant) by various kind of spectroscopic and molecular modeling techniques. Our findings suggest that content of the secondary structure, tertiary structure, florophor environment‚ hydrophobicity Sox2 changes under different environmental conditions. we concluded that the ionic strength changes the protein structure sox2. Been reviewed situations can be used for the design of anti-cancer drugs.

کلیدواژه ها:

Sox2 ، ESC ، spectroscopy ، protein stability ، thermodynamic parameters