Downregulation of HDPR1 is associated with poor prognosis and affects expression levels of p120-catenin and beta-catenin in nonsmall cell lung cancer.
HDPR1 (human homologue of Dapper) is considered as a Dishevelled (DVL) antagonist in WNT signaling. We recently reported that DVL was associated with cytoplasmic accumulation of beta-catenin in nonsmall cell lung cancer (NSCLC). Whether cytoplasmic accumulation of beta-catenin is correlated with HDPR1 is unclear. Xenopus Dapper (XDpr) was found to stabilize p120-catenin (p120ctn) in Xenopus embryogenesis. However, whether HDPR1 can regulate p120ctn expression level is not reported. Furthermore, how HDPR1 influences invasiveness in lung carcinogenesis is also not well understood. In this study, our aims were to explore the effects of HDPR1 on the lung carcinogenesis and to examine the relationship among HDPR1, beta-catenin, and p120ctn. Immunohistochemical analysis in 120 NSCLC tissues showed that HDPR1 was significantly lower in 82 specimens (68.3%). Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blotting analysis showed that the mRNA and protein expression of HDPR1 were lower in tumor tissues as compared to corresponding nontumorous tissues. Moreover, reduced HDPR1 expression was related to the clinicopathological factors and was an independent risk factor for prognosis of the patients with NSCLC. In addition, HDPR1 expression was also associated with the expression of p120ctn and beta-catenin in lung cancer tissues. Knockdown of HDPR1 gene enhanced the invasive ability of lung cancer cells, which was dependent on p120ctn and independent of beta-catenin. In conclusion, the function of HDPR1 on regulating p120ctn may play an important role in human lung carcinogenesis. Restoration of HDPR1 gene may be a new therapeutic target of lung cancer.
Yang
Zhi-Qiang
ZQ
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Heping District, Shenyang, China.
Zhao
Yue
Y
Liu
Yang
Y
Zhang
Jun-Yi
JY
Zhang
Sheng
S
Jiang
Gui-Yang
GY
Zhang
Peng-Xin
PX
Yang
Lian-He
LH
Liu
Di
D
Li
Qing-Chang
QC
Wang
En-Hua
EH
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D051177:Catenins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D051176:beta Catenin / Q000378:metabolism*; D000095002:Delta Catenin
D048868:Adaptor Proteins, Signal Transducing; D051177:Catenins; C491683:DACT1 protein, human; D009687:Nuclear Proteins; D051176:beta Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human