Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer

Abstract

FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.

Role of FAT1 in health and disease (Review)

“…Wang et al (107) used immunohistochemical analysis to detect FAT1 and β-catenin protein expression in ductal carcinoma in situ (DCIS) and IDC, revealing that, compared with in DCIS, the expression levels of FAT1 and β-catenin in IDC were significantly decreased. Additionally, loss of FAT1 expression was associated with higher histological grade and worse lymph node status in human breast cancer (107,108). In addition, FAT1 and β-catenin expression in DCIS and IDC were positively correlated with each other.…”

“…In addition, FAT1 and β-catenin expression in DCIS and IDC were positively correlated with each other. FAT1(-), β-catenin(-) or FAT1(-)/β-catenin(-) suggested a worse disease-free survival rate and prognosis in patients with breast cancer (107). The loss of FAT1 and β-catenin was associated with breast cancer progression, aggressive behavior and a poor prognosis, but the underlying mechanisms between the low expression levels of FAT1 in breast cancer and the Wnt/β-catenin signaling pathway are incompletely understood (107).…”

“…FAT1(-), β-catenin(-) or FAT1(-)/β-catenin(-) suggested a worse disease-free survival rate and prognosis in patients with breast cancer (107). The loss of FAT1 and β-catenin was associated with breast cancer progression, aggressive behavior and a poor prognosis, but the underlying mechanisms between the low expression levels of FAT1 in breast cancer and the Wnt/β-catenin signaling pathway are incompletely understood (107). FAT1 alone or in combination with β-catenin may be a valuable biomarker for predicting the prognosis of patients with breast cancer (107).…”

“…Notable progress has been made regarding the role of FAT1 in breast cancer drug resistance. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) have been demonstrated to be effective in treating numerous types of cancer, such as breast cancer (107), melanoma (109) and pancreatic cancer (110). However, the incidence of drug resistance in cancer is increasing, and the understanding of the mechanisms involved remains limited.…”

FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair

“…identified FAT1 as a candidate tumor-suppressor gene which is able to suppress cancer cell growth by binding β-catenin and antagonizing its nuclear localization in glioblastoma (GBM) ( 8 ). Similarly, in breast cancer, it has been reported that the loss of FAT1 was associated with progression, aggressive behavior, poor prognosis, and cyclin-dependent kinase (CDK) 4/6 inhibitor resistance through the Hippo signaling pathway ( 9 , 10 ). The expression of FAT1, as the transcriptional target of E2F1, was frequently downregulated in ESCC tissues and inhibited proliferation, adhesion, and invasion through the MAPK signaling pathway ( 11 , 12 ).…”