FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/β-Catenin Signaling
Authors: Ailin Li
Hua Tian
Zaiyu Hou
Xiupeng Zhang
Lin Cai
Menghua Xie
Jing Zhao
Yingxue Guo
Yuan Miao
Jingduo Li
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: FAM110B; NSCLC; Wnt/β-catenin signaling; invasion; proliferation.
Affiliations: Department of Pathology, The College of Basic Medical Sciences and The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China., Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Abstract:  Purpose: FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database, we found that FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B playing in NSCLC needs to be further investigated. Patients and methods: Online databases and immunohistochemistry were used to predict the expression and prognostic value of FAM110B in NSCLC samples. Immunofluorescence staining was used to investigate the subcellular distribution of FAM110B. Western blot, MTT, colony formation, and matrigel invasion assay were used to detect the expression and the effect of FAM110B on mediating proliferation and invasion in NSCLC cell lines. Results: In this study, immunohistochemistry results showed that FAM110B expression significantly correlated with early TNM staging (P=0.020) and negative regional lymph node metastasis (P=0.006). Kaplan-Meier survival analysis found that the median survival time of patients with positive FAM110B expression (56.181±2.348 months) was significantly longer than those with negative FAM110B expression (47.701±2.997 months, P=0.024). Moreover, overexpression of FAM110B inhibited the proliferation and invasion of A549, H1299, and LK2 cell lines. Conversely, FAM110B RNAi exerted opposite effects in the above cell lines. Furthermore, FAM110B overexpression downregulated the active β-catenin, phosphorylation of GSK-3β (p-GSK-3β), cyclin B1, cyclin D1, MMP2, and MMP7, and upregulated the phosphorylation of β-catenin (p-β-catenin) in A549 and H1299 cells. Besides, the FAM110B-induced depressions of p-GSK-3β and active β-catenin were reversed after being treated with Wnt/β-catenin inhibitor, XAV-939. Conclusion: In summary, our results demonstrated that the overexpression of FAM110B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/β-catenin signaling. Our study reveals the antitumor function of FAM110B in NSCLC and indicates that FAM110B is a potential therapeutic target. 

Retracted: No

PubPeer comments:
 Figure 3C includes some bands which share unexpected similarities, although the images are obviously not identical. I am concerned that they share the same origin. Other readers on social media share these concerns. Could the authors provide the uncropped original images to address these concerns? *** ![file] *** Contrast adjusted ![file] *** Full figure ![file] , 
 ![file] ![file] Here s original data. They are obviously not shareing the same origin. Note the date and time of these photos. , 
 #2 Dear Dr. Miao, I am not quite sure what we are looking at here. Could you possibly give a bit more context to these scans? If I am reading the paper correctly, there should have been numerous other bands on these gels. Where are, for example, the loading controls? ![file] And where is the size ladder? (Or controls?) Moreover, I do not really understand why we are not seeing the edges of the blot. Have these bands been scanned and then electronically been transferred to a uniform background? It seems as if the background immediately around the bands is significantly darker than is the rest of the scan. Perhaps you could help us understand the work flow for these images? ,