PDF(Pubmed)
Abstract：
Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.
摘要：
基质硬度在各种生物学环境中有效促进恶性表型。因此,鉴定参与机械力信号传导到下游生化信号传导的基因表达将大大有助于鼻咽癌(NPC)治疗的进展.在本研究中,我们检测到cortactin（CTTN）在基质刚度诱导的细胞迁移中起着不可或缺的作用，入侵,和invadopodia形成。癌症研究的进展突出表明，失调的可变剪接作为致癌驱动因素有助于癌症进展。然而,WT-CTTN或剪接变体(SV1-CTTN或SV2-CTTN)是否调节基质僵硬度诱导的恶性表型尚不清楚.我们证明WT-CTTN表达的改变调节了基质刚度诱导的细胞迁移，入侵,和invadopodia形成。考虑到剪接因素可能通过正反馈循环驱动癌症进展，我们分析并展示了剪接因子PTBP2和TIA1如何调节WT-CTTN的产生。此外，我们确定高刚度激活PTBP2表达。一起来看,我们的发现表明，PTBP2-WT-CTTN水平在硬化后增加，然后促进细胞迁移，入侵,和NPC中的invadadopodia形成。
