Biochemical and Biophysical Research Communications
FAT10 promotes the invasion and migration of breast cancer cell through stabilization of ZEB2
Introduction
Breast cancer (BC) is currently the most common form of cancer, and is the fifth leading cause of mortality among women worldwide [1,2]. With the advance of knowledge, breast cancer is clinically divided into three major molecular subtypes, including luminal, HER2-positive, and triple-negative breast cancer [3,4]; distant metastases are the cause of about 90% of deaths in patients with BC [5]. Thus, better understanding of the molecular mechanisms involved in BC metastasis may be helpful in developing therapeutic strategies for breast cancer.
Human Leukocyte Antigen (HLA)-F adjacent transcript 10 (FAT10), also known as Ubd, which is a member of the ubiquitin-like (UBL) modifier family and contains two UBL moieties fused in tandem [6,7]. Similar to other UBL proteins, FAT10 covalently modifies target substrates via a C-terminal Gly-Gly motif and has been involved in many cellular process [8,9]. Emerging evidence has identified FAT10 as a positive regulator of oncogenes and negative regulator of tumor suppressors in a variety of cancer types [[10], [11], [12], [13]]. For instance, high expression of FAT10 notably correlates with metastasis and indicates poor prognosis in hepatocellular carcinoma [12]. However, the clinical significance and potential role of FAT10 in breast cancer is largely unknown.
Here, we found that high FAT10 level is closely related with progression and poor outcome of patients with breast cancer. Further, our results showed that knockdown of FAT10 dramatically suppressed the migration, invasion and EMT of breast cancer cells. Moreover, we confirmed that FAT10 directly interacted with zinc finger E-box binding homeobox 2 (ZEB2), a crucial repressor of EMT progression in diverse cancers including BC [[14], [15], [16]], and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Thus, FAT10 may become a new therapeutic target or clinical biomarker for metastatic breast cancer.
Section snippets
Patients and samples
The adjacent normal and cancerous breast tissue samples from were obtained from 120 BC patients undergoing resection surgery at the Department of Breast Cancer, The Third Hospital of Nanchang City from 2011 to 2017. All specimens from resection surgery were frozen and stored at −80 °C until required. All tissue samples were obtained with informed consent from patients, and the study protocol has been approved by the institutional review board of The Third Hospital of Nanchang City.
Cell lines and culture conditions
The breast
FAT10 is overexpressed in BC, and its overexpression is positively correlated with poor prognosis of BC
To explore the role of FAT10 in breast cancer, we initially examined their expression in the adjacent normal and cancerous breast tissues. As shown in Fig. 1A and B, the qRT-PCR data revealed that the mRNA level of FAT10 is significantly elevated in BC tissues compared with that in adjacent normal breast tissues. In keeping with the increased FAT10 mRNA, the protein level of FAT10 was significantly higher in BC tissues compared to adjacent normal breast tissues (Fig. 1C). Consistently, the IHC
Discussion
FAT10 is a potent oncogene and plays a crucial role in metastasis of several tumors [12,13,25]. However, no information is currently available on the specific role or molecular mechanism of FAT10 in breast cancer. Here, we found that the expression level of FAT10 was obviously elevated in tumors obtained from patients with BC, compared with that in the adjacent normal breast tissues. Importantly, high FAT10 expression was closely associated with TNM stage, distant metastasis and shorter overall
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgments
None.
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