Granzyme M expressed by tumor cells promotes chemoresistance and EMT in vitro and metastasis in vivo associated with STAT3 activation
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Huiru Wang1, Qing Sun2, Yanhong Wu1, Lin Wang3, Chunxia Zhou1, Wenbo Ma1, Youhui Zhang1, Shengdian Wang4 and Shuren Zhang1
1 Department of Immunology, Cancer Hospital & Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
2 Department of Parasitology, Capital Medical University, Beijing, China
3 Department of Pathology, Cancer Hospital & Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
4 Center of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
Shuren Zhang, email:
Keywords: cancer, granzyme M, chemoresistance, metastasis, epithelial-mesenchymal transition
Received: September 28, 2014 Accepted: January 22, 2015 Published: February 28, 2015
Granzyme M is a serine protease known to be often expressed by natural killer cells and induce target cells apoptosis in combination with perforin. However, we detected granzyme M expression in murine and human cancer cell lines and human tumor samples in our study. Granzyme M increased chemoresistance, colony-formation, cytokine secretion and invasiveness in vitro. Most importantly, granzyme M facilitated tumor growth and metastasis in vivo. Granzyme M induced the epithelial-mesenchymal transition (EMT) in cancer cells associated with STAT3 activation. Our study revealed the role of granzyme M expressed by tumor in chemoresistance, invasion, metastasis and EMT.
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