Abstract
Breast cancer (BC) occurs predominantly in women and leads to numerous deaths every year. The identification of effective therapeutic targets will benefit BC patients and increase the likelihood of finding a cure. Family with similar sequence 84, member B (FAM84B) has been implicated in the progression of many kinds of cancers, but its function in BC remains to be explored. In this study, online database analysis revealed that FAM84B expression was higher in BC patient tissues, especially in luminal BC tissues, than in the corresponding normal tissues; furthermore, increased FAM84B expression was related to poor prognosis. Additionally, western blot (WB) analysis revealed that the FAM84B protein was highly expressed in luminal BC cell lines compared to normal and basal-like BC cell lines. Moreover, clinical BC patient tissues were collected and subjected to WB and immunohistochemical (IHC) analyses, and the results showed that FAM84B was expressed mainly in luminal BC samples. Therefore, to determine the function of FAM84B in luminal BC cells, luminal BC cell lines with FAM84B knockout and overexpression were generated. In addition, the functions of FAM84B were evaluated in vitro (via cell proliferation, wound healing, colony formation and invasion assays) and in vivo (via a subcutaneous xenograft experiment), and the results showed that FAM84B regulated cell proliferation but not cell invasion. Furthermore, the results of RNA sequencing analysis in ZR-75-1 FAM84B knockout and FAM84B-overexpressing cells showed that FAM84B could affect the TNF signaling pathway. Subsequently, WB analysis of death receptor signaling and immunofluorescence (IF) analysis of NF-κB p65 localization revealed that FAM84B affected death receptor signaling and promoted NF-κB p65 nuclear entry. In conclusion, we found that FAM84B promotes luminal BC tumorigenesis through the activation of the NF-κB and death receptor signaling pathways.