Anchoring filament protein ladinin-1 (LAD1) was related to the aggressive progression of breast, lung, laryngeal and thyroid cancers. However, the association of LAD1 with colorectal cancer remained unknown. Here, to determine the relationship of LAD1 with colorectal cancer progression, we explored the effect of LAD1 loss on the malignant features of colorectal cancer cells. We constructed LAD1-depleted cell lines and examined the effect of LAD1 deficiency on the phenotypic and molecular features of colorectal cancer cells in vitro. The function of LAD1 in metastasis in vivo was examined by establishing a spleen-to-liver metastasis mouse model. LAD1 protein expression in colorectal cancer patient specimens was assessed by immunohistochemistry of tumor microarrays. We found that LAD1 was abundant in most colorectal cancer cells. In addition, high expression of LAD1 significantly correlated with poor patient outcome. LAD1 depletion inhibited the migration and invasion of two different colorectal cancer cell lines, SW620 and Caco-2, without affecting their proliferation. In addition, LAD1 loss led to defects in liver metastasis of SW620 cells in the mouse model. Immunohistochemistry of colorectal cancer tissues revealed LAD1 enrichment in metastatic tissues compared to that in primary tumor and normal tissues. These results suggest that LAD1 expression is associated with the metastatic progression of colorectal cancer by promoting the migration and invasion of cancer cells.

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LAD1表达与结直肠癌细胞的转移潜能相关


锚定丝蛋白 ladinin-1 (LAD1) 与乳腺癌、肺癌、喉癌和甲状腺癌的侵袭性进展有关。然而，LAD1 与结直肠癌的关联仍不清楚。在这里，为了确定 LAD1 与结直肠癌进展的关系，我们探讨了 LAD1 缺失对结直肠癌细胞恶性特征的影响。我们构建了 LAD1 缺失细胞系，并在体外检测了 LAD1 缺陷对结直肠癌细胞表型和分子特征的影响。通过建立小鼠脾肝转移模型来研究LAD1在体内转移中的功能。通过肿瘤微阵列的免疫组织化学评估结直肠癌患者标本中的 LAD1 蛋白表达。我们发现 LAD1 在大多数结直肠癌细胞中含量丰富。此外，LAD1 的高表达与患者预后不良显着相关。 LAD1 缺失抑制了两种不同结直肠癌细胞系 SW620 和 Caco-2 的迁移和侵袭，但不影响其增殖。此外，LAD1缺失导致小鼠模型中SW620细胞的肝转移缺陷。结直肠癌组织的免疫组织化学显示，与原发肿瘤和正常组织相比，转移组织中 LAD1 富集。这些结果表明LAD1表达通过促进癌细胞的迁移和侵袭与结直肠癌的转移进展相关。