Background: Breast cancer mortality has been stable or decreasing in the world, its incidence
and recurrence rates have sharply risen worldwide in the recent years.
Objective: To investigate the clinicopathological significance and potential function of GRP78 in the
development and progression of breast cancer. To explore the effects of neoisoliquiritigenin (NISL)
in breast cancer and the underlying mechanism.
Method: GRP78 was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays
(TMAs), and the association between GRP78 levels and clinicopathological factors and prognosis
was analyzed. The functional effects of GRP78 on breast cancer were validated by an MTT
assay, foci formation assay, Matrigel invasion assay and mouse xenograft assay. The effects of
NISL were tested by an MTT assay, apoptosis assay and mouse xenograft assay. A LigandFit algorithm,
ATPase activity assay, western blot and IHC assay were used to discover the underlying
mechanism of the effects of NSIL.
Results: GRP78 was highly expressed in breast cancer cell lines and tissues. In addition, high expression
of GRP78 was correlated to poor outcomes and distant metastasis. Functional experiments
showed that GRP78 promoted breast cancer proliferation and invasion in vitro and in vivo. NISL inhibited
cell proliferation and induced cell apoptosis in breast cancer by directly binding to GRP78 to
regulate the β-catenin pathway.
Conclusion: Taken together, these results highlighted the significance of GRP78 in breast cancer
development and suggested NISL as a natural candidate to inhibit breast cancer by targeting GRP78
and β-catenin signaling.