Abstract
Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.
Highlights
Breast cancer has become one of the cancers with high survival rate
Heparin-binding growth factor (HDGF) is overexpressed in breast cancer and negatively associated with the clinical outcome of patients To uncover the precise role of HDGF in breast cancer, we first examined the DNA copy number of HDGF from the TCGA database
There are no reports on the explicit role of HDGF in the radioresistance of breast carcinoma
Summary
Breast cancer has become one of the cancers with high survival rate. As long as most patients can be detected early and receive standard treatment, the 5-year survival rate is as high as 80%. Breast cancer is still one of the most deadly cancers for women [1, 2]. Diagnosis of breast cancer is more prevalent among women [3, 4]. Surgical resection remains the most effective approach for breast cancer management [5]. Studies have revealed the association of HDGF expression with clinical outcomes of patients with pancreatic cancer [16], gastric cancer [17], hepatocellular carcinoma [18]
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