화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.482, No.1, 35-42, 2017
APBB1 reinforces cancer stem cell and epithelial-to-mesenchymal transition by regulating the IGF1R signaling pathway in non-small-cell lung cancer cells
Amyloid beta precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells. In APBB1-deficient H460 cells with forced overexpression of APBBI, the protein directly interacted with IGF1R beta, enhanced phosphorylation of IGF1R beta/PI3K/AKT pathway(activation) and subsequently induced the phosphorylation of GSK313( inactivation). This phosphorylation stabilized Snaill, a negative regulator of E-cadherin expression, and regulated p-catenin-mediated ALDHI expression, which are representative markers for EMT and CSCs, respectively. In contrast, suppression of APBB1 expression with siRNA yielded the opposite effects in APBB1-rich A549 cells. We concluded that APBB1 partly regulates the expression of ALDHI. We also found that APBB1 regulates activation of nuclear factor-KB, which is involved in reducing various stresses including oxidative stress, which suggests that APBB1 is associated with y-radiation sensitivity. Our findings imply that APBB1 plays an important role in the maintenance of EMT-associated CSC-like properties and gamma-radiation resistance via activation of IGF11213/AKT/GSK313 pathway in lung cancer cells, highlighting APBB1 as a potential target for therapeutic cancer treatment. (C) 2016 Elsevier Inc. All rights reserved.