Yamei Hu1, Xin Li1, Wenwen Xue1, Juan Pang1, Yiwei Meng1, Yan Shen2, Qiang Xu3. 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China. 2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China. Electronic address: shenyan@nju.edu.cn. 3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China. Electronic address: molpharm@163.com.
Abstract
BACKGROUND: Understanding the function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancers. Here, we studied the contribution of basal autophagy in human liposarcoma. METHODS: The levels of basal autophagy were analyzed by measuring autophagy-related protein expression and autophagosome formation. TP53INP2 expression was determined by real-time PCR, western blot and tissue microarray. Genetic inhibition or overexpression of TP53INP2 was performed to examine its effects on autophagic activity and cell growth. RESULTS: Compared with human liposarcoma cell line SW872, low level of basal autophagy were present in SW872-S cells with high malignancy. Moreover, a decrease of TP53INP2 expression was found accompanying liposarcoma malignant progression in cell lines and primary tissues. TP53INP2 expression was required for autophagic activity in liposarcoma cells. Autophagy inhibition with chloroquine suppressed the growth of liposarcoma cells. TP53INP2-related basal autophagy rendered liposarcoma cells to be more resistant to bortezomib-induced inhibition of cell growth. CONCLUSIONS: The results reveal the association of TP53INP2-related basal autophagy with cell growth and malignant progression of human liposarcoma, which helps re-evaluate targeting autophagy for cancer therapy, and suggest that TP53INP2 expression might be used as a prognostic marker to predict human liposarcoma malignancies.
BACKGROUND: Understanding the function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancers. Here, we studied the contribution of basal autophagy in humanliposarcoma. METHODS: The levels of basal autophagy were analyzed by measuring autophagy-related protein expression and autophagosome formation. TP53INP2 expression was determined by real-time PCR, western blot and tissue microarray. Genetic inhibition or overexpression of TP53INP2 was performed to examine its effects on autophagic activity and cell growth. RESULTS: Compared with humanliposarcoma cell line SW872, low level of basal autophagy were present in SW872-S cells with high malignancy. Moreover, a decrease of TP53INP2 expression was found accompanying liposarcoma malignant progression in cell lines and primary tissues. TP53INP2 expression was required for autophagic activity in liposarcoma cells. Autophagy inhibition with chloroquine suppressed the growth of liposarcoma cells. TP53INP2-related basal autophagy rendered liposarcoma cells to be more resistant to bortezomib-induced inhibition of cell growth. CONCLUSIONS: The results reveal the association of TP53INP2-related basal autophagy with cell growth and malignant progression of humanliposarcoma, which helps re-evaluate targeting autophagy for cancer therapy, and suggest that TP53INP2 expression might be used as a prognostic marker to predict humanliposarcoma malignancies.