The small heat shock protein αA-crystallin negatively regulates pancreatic tumorigenesis
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Jifang Liu1,3,*, Zhongwen Luo1,*, Lan Zhang1,*, Ling Wang1,2,4,*, Qian Nie1,4,*, Zheng-Feng Wang2,5,*, Zhaoxia Huang2,4, Xiaohui Hu2,4, Lili Gong1, Andre-Patrick Arrigo1, Xiangcheng Tang1, Jia-Wen Xiang4, Fangyuan Liu1, Mi Deng2, Weike Ji2, Wenfeng Hu2, Ji-Ye Zhu5, Baojiang Chen6, Julia Bridge7, Michael A. Hollingsworth8, James Gigantelli2, Yizhi Liu1, Quan D. Nguyen2, David Wan-Cheng Li1,2,4,8
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, China
2Department of Ophthalmology & Visual Sciences, Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
3Institute of Cancer Research, The Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510095, China
4Key Laboratory of Protein Chemistry and Developmental Biology, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
5Hepatobiliary Surgery Center of Peking University People’s Hospital, Peking University, Beijing 100044, China
6Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA
7Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha, NE 68198, USA
8Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
*These authors have contributed equally to this work
David Wan-Cheng Li, email: firstname.lastname@example.org
Keywords: small heat shock protein, αA, pancreatic cancer, tumor suppression, cancer therapy
Received: June 01, 2016 Accepted: August 14, 2016 Published: August 29, 2016
Our recent study has shown that αA-crystallin appears to act as a tumor suppressor in pancreas. Here, we analyzed expression patterns of αA-crystallin in the pancreatic tumor tissue and the neighbor normal tissue from 74 pancreatic cancer patients and also pancreatic cancer cell lines. Immunocytochemistry revealed that αA-crystallin was highly expressed in the normal tissue from 56 patients, but barely detectable in the pancreatic tumor tissue. Moreover, a low level of αA-crystallin predicts poor prognosis for patients with pancreatic duct adenocarcinoma (PDAC). In the 12 pancreatic cell lines analyzed, except for Capan-1 and Miapaca-2 where the level of αA-crystallin was about 80% and 65% of that in the control cell line, HPNE, the remaining pancreatic cancer cells have much lower αA-crystallin levels. Overexpression of αA-crystallin in MiaPaca-1 cells lacking endogenous αA-crystallin significantly decreased its tumorigenicity ability as shown in the colony formation and wound healing assays. In contrast, knockdown of αA-crystallin in the Capan-1 cells significantly increased its tumorigenicity ability as demonstrated in the above assays. Together, our results further demonstrate that αA-crystallin negatively regulates pancreatic tumorigenesis and appears to be a prognosis biomarker for PDAC.
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