These observations suggested that HYAL1 plays a role in promoting the invasive potential

We demonstrated that forcing expression of HYAL1 in breast cancer cells promoted tumor progression in vitro and in vivo. We therefore provided functional evidence that HYAL1 is oncogenic for breast cancer and functional antagonism of HYAL1 constitutes a potential therapeutic strategy for HYAL1 positive breast cancer. In this study, the eukaryotic expression plasmid pcDNA3.1- HYAL1 was constructed to force HYAL1 expression in breast cancer cell lines MCF7 and ZR-75-30. Our results showed that upregulation of HYAL1 Talazoparib 1207456-01-6 resulted in cell growth increase in vitro and in vivo. It was also identified that HYAL1 expression in bladder cells regulated tumor gowth. These results suggested that HYAL1 expression in tumor cells is required for cell proliferation. Meanwhile, upregulation of HYAL1 expression enhanced the proportion of cells cycling in S phase, which is consistent with Lin et al. and our previous researches. Based on the analysis of cell cycle regulators, HYAL1 affects cell proliferation probably by regulating cell cycle. Our finding that upregulation of HYAL1 in breast cancer cells could enhance the HAase activity significantly, and the HA expression was decreased obviously in vitro, these results identified that HYAL1 could degrade HA. Which was according with previous researches. Interestingly, upregulation of HYAL1 expression enhanced the HAase activity, at the same time, the HA expression was increased in vivo. Lokeshwar et al. found that high level of HA was expression in tumor-associated stroma of HYAL1-sense tumor specimen, but very low HA expression was observed in the stromal compartment of HYAL1-antisense tumor specimens. Which indicated the HYAL1 could induce the stroma cells of tumor to secrete HA, although it could cleave HA. In addition to the effect of HYAL1 on tumor growth, its effects on tumor cell migration and invasion are interesting. Our previous researches showed that breast cancer cells with higher HAase expression, exhibit significantly higher invation ability through matrigel than those cells with lower HAase expression. Knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell invasion. HYAL1 was also an independent prognostic indicator for predicting biochemical recurrence in prostate cancer and increased metastatic potential in a prostate cancer model. In the current study, we demonstrated that upregulation of HYAL1 expression in MCF7 and ZR-75-30 cells resulted in high metastasis potential and altered several functions such as cell migration and invasion in vitro.