Abstract
Background
To explore the expression of frizzled related protein (FRZB) in triple-negative breast
cancer (TNBC) and role of FRZB in TNBC cell growth and invasion.
Methods
Breast cancer clinical data were downloaded from the Cancer Genome Atlas. FRZB and
early growth response 1 (EGR1) mRNA levels in TNBC were measured by quantitative real-time
polymerase chain reaction. FRZB protein level was measured by immunohistochemistry
and western blot. Proliferation, migration, and invasion of TNBC cells were detected
by colony formation, wound healing, and transwell assay, respectively. The protein
levels of EGR1, E-cadherin, N-cadherin, Snail, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3
were measured by western blot. JASPAR was used to predict the binding site of FRZB
and EGR1. The binding ability of FRZB and EGR1 was verified by dual-luciferase reporter
gene assay and chromatin immunoprecipitation assay.
Results
FRZB was low expressed in TNBC tissues and cells. Silencing FRZB promoted cell proliferation,
migration, invasion, and EMT and activated JAK/STAT pathway in MDA-MB-468 and MDA-MB-231
cells, but overexpression of FRZB acted opposite effects in MDA-MB-468 and MDA-MB-231
cells. EGR1 was low expressed in TNBC samples and positively correlated with FRZB.
Moreover, EGR1 could recover the promotion of silencing FRZB on cell proliferation,
migration, invasion, and JAK/STAT pathway in MDA-MB-468 cells, but silencing EGR1
led to the opposite results in MDA-MB-231 cells.
Conclusion
FRZB was low expressed in TNBC and was regulated by EGR1, and FRZB inhibited TNBC
cell growth and invasion by regulating the JAK/STAT3 pathway.
Keywords
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Article Info
Publication History
Published online: June 02, 2022
Accepted:
May 30,
2022
Received in revised form:
March 28,
2022
Received:
December 30,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
