The small heat shock protein αA-crystallin negatively regulates pancreatic tumorigenesis.

// Jifang Liu 1, 3, * , Zhongwen Luo 1, * , Lan Zhang 1, * , Ling Wang 1, 2, 4, * , Qian Nie 1, 4, * , Zheng-Feng Wang 2, 5, * , Zhaoxia Huang 2, 4 , Xiaohui Hu 2, 4 , Lili Gong 1 , Andre-Patrick Arrigo 1 , Xiangcheng Tang 1 , Jia-Wen Xiang 4 , Fangyuan Liu 1 , Mi Deng 2 , Weike Ji 2 , Wenfeng Hu 2 , Ji-Ye Zhu 5 , Baojiang Chen 6 , Julia Bridge 7 , Michael A. Hollingsworth 8 , James Gigantelli 2 , Yizhi Liu 1 , Quan D. Nguyen 2 , David Wan-Cheng Li 1, 2, 4, 8 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, China 2 Department of Ophthalmology & Visual Sciences, Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA 3 Institute of Cancer Research, The Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510095, China 4 Key Laboratory of Protein Chemistry and Developmental Biology, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China 5 Hepatobiliary Surgery Center of Peking University People’s Hospital, Peking University, Beijing 100044, China 6 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA 7 Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha, NE 68198, USA 8 Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA * These authors have contributed equally to this work Correspondence to: David Wan-Cheng Li, email: dwli1688@hotmail.com Keywords: small heat shock protein, αA, pancreatic cancer, tumor suppression, cancer therapy Received: June 01, 2016      Accepted: August 14, 2016      Published: August 29, 2016 ABSTRACT 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.