Role of SQSTM1/p62 in bortezomib-induced apoptosis of human colorectal cancer cells

Ting-Han Chen(陳廷翰)1, Tzu-Yen Tseng2, Meng-Hsiu Wu2, and Jui-I Chao1,2,3,*

1Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan

2Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan

3Center For Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan 

Colorectal cancer is the one of the major causes and mortality of cancers in worldwide. Bortezomib is the first synthetic proteasome inhibitor that use to treat cancers. SQSTM1 is an  autophagy receptor that can target substrates for entry into selective autophagy pathway. Bortezomib has been shown to induced apoptosis in human cancer cells. However, the role of SQSTM1 in regulating bortezomib-induced apoptosis is still unclear. Here, we show that treatment with bortezomib increased the phosphorylation of SQSTM1 at Ser403 and total SQSTM1 protein levels in human CRC cells. Interestingly, the gene knockout of SQSTM1 gene reduce the bortezomib-induced cell death in CRC cells. The depletion of SQSTM1 decreased the apoptotic protein including total p53, p-p53(Ser15), PARP cleavage, and active caspase 3 by treatment with bortezomib. In contrast, re-expression of SQSTM1 by transfection with a SQSTM1-GFP expressed vector in the SQSTM1 knockout cells increased the bortezomib–induced cell death. Taken together, we suggest that SQSTM1 plays an important role in regulating bortezomib-induced apoptosis in human CRC cells.

Key words: Colorectal cancer, Bortezomib, Apoptosis, Selective autophagy, SQSTM1