Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma
Authors: Min Zheng
Ya-Ling Tang
Sha-Sha Wang
Xin Pang
Mei Zhang
Jia-Shun Wu
Jing-Biao Wu
Ya-Jie Tang
Xiao Yang
Xin-Hua Liang
Li Li
Journal: Frontiers in Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: cathepsin D (CTSD); cytoskeletal organization; invasion frontier; perineural invasion (PNI); salivary adenoid cystic carcinoma (SACC).
Affiliations: State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China., National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China., Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China., Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China., Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China.

Abstract:  Objective: Cathepsin D (CTSD) is a pivotal orchestrator in the occurrence and development of tumors. Recently, CTSD was detected in salivary adenoid cystic carcinoma (SACC). However, its functional role in perineural invasion (PNI) of SACC remained elusive. We conducted the present study to detect the expression of CTSD in SACC, analyze the correlation between CTSD expression and prognosis of SACC patients and elucidate the role of CTSD in occurrence of PNI in SACC to lay the foundation for further studies. Methods: Immunohistochemical analysis was conducted to assess CTSD and Ki67 expression in 158 SACC samples and 20 normal salivary gland samples adjacent to carcinoma. Meanwhile, the correlation between CTSD and PNI of SACC specimens was analyzed using Wilcoxon test. QRT-PCR, immunofluorescence and western blot analysis were used to examine the levels of CTSD mRNA and protein in SACC-LM cell line. SiRNA-mediated CTSD silence was performed. Scratch wound healing assay, transwell invasion assay and DRG co-culture assay of PNI was used to detect the ability of migration, invasion and PNI. FITC-phalloidin was used to detect cytoskeletal organization. Results: Our data demonstrated that the positive expression of CTSD was observed in 74.1% (117/158) of SACC cases, and the expression of CTSD was significantly correlated with the PNI (p &lt; 0.05). The ability of migration, invasion, and PNI could be inhibited significantly by siRNA-mediated CTSD silence (p &lt; 0.01). Furthermore, siRNA-mediated CTSD silence inhibited cytoskeletal organization and pseudo foot formation in SACC-LM cells. Conclusion: Our results suggested that an association between PNI and expression of CTSD existed. CTSD may promote PNI of SACC accompanied by cytoskeletal organization and pseudo foot formation. 

Retracted: No

PubPeer comments:
 Figures 4A and 4C appear to have some images which overlap. *** Enhanced contrast  ***  , 
 Thanks for your information! We had carefully checked the figures and found that the images were different. , 
 #2 Thank you for your reply. As this is clearly not true, I will suggest the journal investigate. This lab appears to have more than a [dozen papers] with similar concerns. , 
 The authors apparently had a change of heart. Published online 2021 Jun 23. In the original article, there was a mistake in Figure 4 as published. In Figures 4A, C , we put the wrong picture due to carelessness. The correct Figure 4 appears below.  The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. ,