BCSC-1 suppresses human breast cancer metastasis by inhibiting NF-κB signaling

Abstract

Breast cancer suppressor candidate-1 (BCSC-1; also termed von Willebrand factor A domain containing 5A and LOH11CR2A) is a newly identified candidate tumor suppressor gene that has been implicated in several types of cancer in previous studies. However, there have been few reports about the association between BCSC-1 and human breast cancer in recent years. In the present study, the expression of BCSC-1 in breast cancer was determined by immunohistochemistry (IHC) staining of tissue microarrays and clinical tissue specimens. Subsequently, BCSC-1 gene expression was evaluated in different breast cancer cell lines by quantitative polymerase chain reaction and the MDA-MB-231 cell line was selected for further use in subsequent experiments, due to its low BCSC-1 expression. An MDA-MB-231 cell line with stable overexpression of BCSC-1 was established through transfection with plasmid containing the BCSC-1 gene, and then screening for G418 resistance. Wound-healing, migration and invasion assays were conducted to detect the effect of BCSC-1 on MDA-MB-231 cells. Furthermore, changes in matrix metalloproteinases (MMPs), osteopontin (OPN) and the nuclear factor-κB (NF-κB) pathway were detected in the current study. Additionally, stable silencing of BCSC-1 expression in MCF-7 cells was performed using a lentivirus. The results of IHC indicated that BCSC-1 is expressed at low levels in breast cancer tissues compared with in normal breast tissue. Results of the wound healing, migration and invasion assays demonstrated that BCSC-1 overexpression reduced the metastasis ability of MDA-MB-231 cells in vitro. Further research confirmed that the BCSC-1 overexpression reduced the expression levels of MMP7, MMP9 and OPN, and the phosphorylation of NF-κB p65. Furthermore, inhibition of BCSC-1 via lentivirus-mediated RNA interference revealed that the downregulation of BCSC-1 increased the invasive ability of MCF-7 cells. In summary, the results demonstrated that BCSC-1 is expressed at low levels in breast cancer tissues, and that it can suppress human breast cancer cell migration and invasion, potentially altering the expression of MMP7, MMP9, OPN, and the activity of the NF-κB pathway. Therefore, BCSC-1 may be useful as a biomarker for the treatment of breast cancer in the future.

Identification of VWA5A as a novel biomarker for inhibiting metastasis in breast cancer by machine-learning based protein prioritization

“…In our proteomics discovery data, the expression of VWA5A gradually decreased as the clinical features of each group worsened, from NM, LM, and finally M groups, which was in line with previous studies that designated VWA5A as a tumor suppressor 18 . Additional biological network-based feature selection also suggested this molecule as the reliable biomarker representing metastasis-prone BCs.…”

Chromosome-Level Analysis of the Pelochelys cantorii Genome Provides Insights to Its Immunity, Growth and Longevity

“…Notably, among these duplicate genes, we characterized several candidates associated with tumor suppression, growth and age based on database annotation, which might play a significant role in exceptional longevity. VWA5A, also known as BCSC-1 or LOH11CR2A, may be useful as a biomarker for the treatment of breast cancer and has been revealed to suppress human-breast-cancer cell migration and invasion, potentially altering the expression of MMP7, MMP9 and OPN, and the activity of the NF-κB pathway [45]. ABCG2, also known as breast-cancer resistance protein (BCRP), is a multidrug-resistant protein that is a member of the ATP-binding cassette family of drug transporters [46].…”

Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer

“…NOTCH family proteins function as receptors for membrane-bound ligands Jagged-1, Jagged-2, and Delta-1 to regulate cell fate and development through the formation of transcriptional regulator complexes [ 24 , 25 ]. Aberrant NOTCH expression has been linked to the progression of various types of cancer [ 66 ]. Additionally, various EGF-like repeat-containing proteins, such as fibulin-2, implicated in embryonic development and tissue homeostasis [ 26 , 67 ] were aligned to the AFP 14–20 segment.…”