LAMC2, as a unique chain in the Laminin 5 molecule, has been found to be associated with malignant metastases in some cancers. However, the roles and mechanisms by which LAMC2 affects the migration and invasion of pancreatic cancer cells remain unclear. First, we found that laminin 5/LAMC2 and its receptors were highly expressed in pancreatic cancer tissues and cells. Then, we investigated the effects of LAMC2 on pancreatic cancer cell migration/invasion and extracellular (pHe). We also demonstrated that LAMC2 phosphorylated Akt-Ser473 to promote the expression, activity and cell membrane accumulation of NHE1 within pancreatic cancer cells. So we speculated that LAMC2 modulated the pHe to promote migration and invasion of pancreatic cancer cells. Additionally, our data also showed that LAMC2/NHE1 resulted in altered cell morphology and aberrant expression of mesenchymal markers. The function of actin-binding proteins (ABPs) were affected by LAMC2/NHE1 signaling. LAMC2/NHE1 signaling generated extracellular acidification to induce dynamic actin-dependent pseudopodial formation and EMT programs that promote tumor cell invasion in pancreatic cancer cells. Therefore, we found that LAMC2 was responsible for generating the extracellular acidic conditions that mediated invasion of pancreatic cancer cells by activating Akt/NHE1 signaling. LAMC2 is a characteristic prognostic and therapeutic agent of PDCA.

中文翻译：

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LAMC2通过调节AKT依赖性NHE1活性来调节微环境的酸度，从而促进胰腺癌细胞的侵袭和迁移。

作为层粘连蛋白5分子中的独特链，LAMC2已发现与某些癌症的恶性转移有关。然而，LAMC2影响胰腺癌细胞迁移和侵袭的作用和机制仍不清楚。首先，我们发现层粘连蛋白5 / LAMC2及其受体在胰腺癌组织和细胞中高表达。然后，我们调查了LAMC2对胰腺癌细胞迁移/侵袭和细胞外（pHe）的影响。我们还证明，LAMC2磷酸化Akt-Ser473，以促进胰腺癌细胞内NHE1的表达，活性和细胞膜积聚。因此，我们推测LAMC2调节pHe以促进胰腺癌细胞的迁移和侵袭。另外，我们的数据还显示，LAMC2 / NHE1导致细胞形态改变和间充质标记物异常表达。肌动蛋白结合蛋白（ABPs）的功能受到LAMC2 / NHE1信号传导的影响。LAMC2 / NHE1信号产生细胞外酸化，从而诱导动态肌动蛋白依赖性假足形成和EMT程序，从而促进胰腺癌细胞中肿瘤细胞的侵袭。因此，我们发现LAMC2负责通过激活Akt / NHE1信号产生介导胰腺癌细胞侵袭的细胞外酸性条件。LAMC2是PDCA的特征性预后和治疗剂。LAMC2 / NHE1信号产生细胞外酸化，从而诱导动态肌动蛋白依赖性假足形成和EMT程序，从而促进胰腺癌细胞中肿瘤细胞的侵袭。因此，我们发现LAMC2负责通过激活Akt / NHE1信号产生介导胰腺癌细胞侵袭的细胞外酸性条件。LAMC2是PDCA的特征性预后和治疗剂。LAMC2 / NHE1信号产生细胞外酸化，从而诱导动态肌动蛋白依赖性假足形成和EMT程序，从而促进胰腺癌细胞中肿瘤细胞的侵袭。因此，我们发现LAMC2负责通过激活Akt / NHE1信号产生介导胰腺癌细胞侵袭的细胞外酸性条件。LAMC2是PDCA的特征性预后和治疗剂。