HSP70 Regulate Invadopodia-associated Proteins Expression In OSCC

Objective: Exploring the role of HSP70 in the invasion and metastasis of OSCC and related molecμlar events will help us further understand the occurrence and development of OSCC.Methods: The expression of HSP70 and invadopodia-related protein(HIF1α,Cortactin,MMP14,MMP2)in OSCC was measured by immunohistochemical method,and the correlation of HSP70,HIF1α,Cortactin,MP14 and MMP2 proteins was analyzed by bioinformatics method.CCK8 and EDU assay were used to detect the toxicity of HSP70 inhibitors on OSCC cells.The effects of HSP70 inhibitors on migration and invasiveness of OSCC cells were examined by Wound Healing Assay and Transwell Assay.The protein expressions of HIF1α,Cortactin,MMP14 and MMP2 in OSCC cells treated with HSP70 inhibitor under normoxic and hypoxic conditions were measured by Western Blot.Resμlts:1.Immunohistochemical resμlts showed that the expressions of HSP70,HIF-1 α,Cortactin,MMP14 and MMP2 in OSCC tissues were higher than those in corresponding paracancerous tissues,and the expression levels of HSP70 were significantly positively correlated with HIF-1 α,Cortatin,MMP14 and MMP2(P < 0.01).2.Bioinformatics resμlts showed that the expressions of HSPA4 and HIF1 A,HIF1A and CTTN,CTTN and MMP14,MMP14 and MMP2 were significantly positively correlated(P < 0.01).3.Inhibition of HSP70 significantly reduced the activity and proliferation of OSCC cells(P < 0.001).4.Inhibition of HSP70 significantly reduced the migration and invasiveness of OSCC cells(P < 0.001).5.After treatment with HSP70 inhibitor,the expressions of HIF1α,Cortatin,MMP14 and MMP2 proteins in OSCC cells decreased.Inhibition of HSP70 decreased the protein expression of HIF1α,Cortactin and MMP14 in OSCC cells under hypoxia.Conclusion: HSP70 、 HIF1α 、 Cortatin 、 MMP14 、 MMP2 were highly expressed in OSCC,and HSP70 was significantly correlated with HIF1α、Cortatin、MMP14、MMP2.Inhibition of HSP70 significantly reduced the activity,proliferation,migration and invasiveness of OSCC cells,suggesting that HSP70 may inhibit the invasion and metastasis of OSCC cells by decreasing the expression level of invadopodia-related proteins.