Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC.

胰腺导管腺癌（PDAC）是一种恶性肿瘤，由于高度转移，预后很差。细胞迁移是转移级联反应的重要步骤，它可使癌细胞向靶组织扩散。最近的研究强烈表明，在基质的肿瘤重塑过程中，具有生物活性的弹性蛋白肽（也称为弹性蛋白或弹性蛋白衍生的肽（EDP））在细胞外微环境中释放。EDP​​通过与其膜受体核糖体蛋白SA（RPSA）相互作用来刺激癌细胞迁移。其他膜蛋白（例如离子通道）也参与癌细胞的迁移。最近显示，瞬时受体电位褪黑素相关7（TRPM7）通道调节PDAC细胞迁移和侵袭。这项工作的目的是研究EDP对人胰腺癌细胞TRPM7通道的影响。我们显示，使用博登室测定法，EDP促进MIA PaCa-2细胞迁移。用靶向TRPM7的siRNA转染的细胞不能响应EDP迁移，表明TRPM7调节了这些肽诱导的细胞迁移。此外，EDP能够刺激由膜片钳记录的TRPM7电流。最后，我们显示TRPM7通道和RPSA受体共定位在人胰腺癌细胞的质膜上。两者合计，我们的数据表明TRPM7 / RPSA复合物调节人类胰腺癌细胞的迁移。该复合物可能是PDAC中有希望的治疗靶标。用靶向TRPM7的siRNA转染的细胞不能响应EDP迁移，表明TRPM7调节了这些肽诱导的细胞迁移。此外，EDP能够刺激由膜片钳记录的TRPM7电流。最后，我们显示TRPM7通道和RPSA受体共定位在人胰腺癌细胞的质膜上。两者合计，我们的数据表明TRPM7 / RPSA复合物调节人类胰腺癌细胞的迁移。该复合物可能是PDAC中有希望的治疗靶标。用靶向TRPM7的siRNA转染的细胞不能响应EDP迁移，表明TRPM7调节了这些肽诱导的细胞迁移。此外，EDP能够刺激由膜片钳记录的TRPM7电流。最后，我们显示TRPM7通道和RPSA受体共定位在人胰腺癌细胞的质膜上。两者合计，我们的数据表明TRPM7 / RPSA复合物调节人类胰腺癌细胞的迁移。该复合物可能是PDAC中有希望的治疗靶标。我们发现TRPM7通道和RPSA受体共定位在人胰腺癌细胞的质膜上。两者合计，我们的数据表明TRPM7 / RPSA复合物调节人类胰腺癌细胞的迁移。该复合物可能是PDAC中有希望的治疗靶标。我们发现TRPM7通道和RPSA受体共定位在人胰腺癌细胞的质膜上。两者合计，我们的数据表明TRPM7 / RPSA复合物调节人类胰腺癌细胞的迁移。该复合物可能是PDAC中有希望的治疗靶标。