Late-stage inhibition of autophagy enhances calreticulin surface exposure
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Dan-Dan Li1,*, Bo Xie2,*, Xiao-Jun Wu3,*, Jing-Jing Li1, Ya Ding1, Xi-Zhi Wen1, Xing Zhang1, Shu-Guang Zhu4,5, Wei Liu4,5, Xiao-Shi Zhang1, Rui-Qing Peng1
1Biotherapy Center, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
2Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
3Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
4Department of Hepatic Surgery, Liver Transplant Center, Third Affiliated Hospital of Sun Yat-Sen University, TianHe District, Guangzhou 510630, China
5Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
*These authors contributed equally to this work
Rui-Qing Peng , email: [email protected]
Xiao-Shi Zhang , email: [email protected]
Keywords: calreticulin, autophagy, endoplasmic reticulum stress, mTOR, chemotherapy induced immunogenic cell death
Received: September 01, 2015 Accepted: October 13, 2016 Published: November 04, 2016
Calreticulin (CRT) exposure on the cell surface is essential for inducing immunogenic cell death by chemotherapy. Recent studies have shown conflicting effects of chemotherapy-induced autophagy on CRT exposure in cancer cells. Our data revealed that surface-exposed CRT (Ecto-CRT) emission was attenuated by inhibition of autophagy at early stages; however, inhibition of autophagy at late stages resulted in increased Ecto-CRT. Furthermore, neither autophagy activation nor endoplasmic reticulum (ER) stress induction alone was sufficient for CRT surface exposure. Moreover, chemotherapeutic agents that only activated autophagy without inducing ER stress could not increase Ecto-CRT; therefore, combined use of an autophagy activator and ER stress inducer could effectively promote CRT translocation to the plasma membrane. Together, our results highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells.
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