Expression of LPA2 is associated with poor prognosis in human breast cancer and regulates HIF-1α expression and breast cancer cell growth.

Breast cancer (BC) generally exhibits poor prognosis owing to its invasive and metastatic characteristics and is the leading cause of cancer-related deaths in women worldwide. Lysophosphatidic acid receptor 2 (LPA2) and hypoxia inducible factor-1α (HIF-1α) were found to be correlated with BC invasion and metastasis, respectively. However, the effect of LPA2 on BC in Chinese women has not yet been reported, nor have the overall survival and prognostic significance of LPA2 or its association with HIF-1α in BC. In the present study, we assessed the effect of LPA2 on HIF-1α expression, on overall survival and prognostic significance in BC in Chinese women, and on cell proliferation, migration and invasion in MCF-7 BC cells in vitro. The data showed that LPA2 and HIF-1α protein expression levels were higher in the BC tissue specimens and that LPA2 expression was significantly associated with menopausal status (postmenopausal), nodal metastasis and tumor-node-metastasis (TNM) stage, whereas HIF-1α expression was significantly associated with estrogen receptor status, nodal metastasis and TNM stage. Furthermore, LPA2 and HIF-1α expression were positively correlated (r=0.562; P<0.001). LPA2 and HIF-1α protein levels were associated with shorter overall patient survival according to univariate analysis (log-rank test; P<0.001), and nodal metastasis, TNM stage, LPA2 and HIF-1α expression were independent prognostic predictors in patients as determined by multivariate analysis (P<0.05). In vitro, the data suggested that LPA2 affected HIF-1α expression and LPA2 overexpression or knockdown resulted in increased or inhibited tumor cell proliferation, migration and invasion, respectively. In conclusion, our data demonstrated that LPA2 expression was associated with HIF-1α expression and that a high level of LPA2 was associated with shorter overall survival and was an independent prognostic predictor for BC in Chinese women. Furthermore, LPA2 showed the ability to regulate the cell proliferation, migration and invasion of BC cells.

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