FAM96A and FAM96B function as new tumor suppressor genes in breast cancer through regulation of the Wnt/ß-catenin signaling pathway.
Life Sci
; 308: 120983, 2022 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-36165859
ABSTRACT
AIMS:
Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Some studies have shown that FAM96A and FAM96B are significantly down-regulated in human gastrointestinal stromal tumors, colon cancer, and liver cancer. However, the molecular mechanisms of FAM96A/B in breast cancer are unknown. This work aims to explore the roles of FAM96A/B in breast cancer progression. MAINMETHODS:
Specific siRNAs were used to down-regulate FAM96A/B expression, and recombinant plasmids were used to up-regulate FAM96A/B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. The relationships among FAM96A/B, EMT and Wnt/ß-catenin pathway were determined by analyzing expression changes of classical markers. KEYFINDINGS:
We found that FAM96A/B expression was down-regulated in breast cancer. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and caused cell cycle arrest. Conversely, FAM96A/B knockdown exhibited the opposite effects. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/ß-catenin pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/ß-catenin pathway. Furthermore, a Wnt pathway inhibitor, XAV-939 reversed the promoting effects of FAM96A/B knockdown on breast cancer progression.SIGNIFICANCE:
Our findings suggest that FAM96A/B may function as new tumor suppressor genes and inhibit breast cancer progression via modulating Wnt/ß-catenin pathway, which can provide the potential markers for breast cancer diagnosis and therapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Wnt Signaling Pathway
Limits:
Female
/
Humans
Language:
En
Journal:
Life Sci
Year:
2022
Document type:
Article
Affiliation country:
China
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS