LAD1 expression is associated with the metastatic potential of colorectal cancer cells
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RESEARCH ARTICLE
Open Access
LAD1 expression is associated with the metastatic potential of colorectal cancer cells Byul Moon1,2, Suk-Jin Yang1,3, Seong Min Park1,4, Sang-Hyun Lee5, Kyu Sang Song6, Eun-Jeong Jeong5,7, Mijin Park1,2, Jang-Seong Kim5,2, Young Il Yeom1,2 and Jung-Ae Kim1,2*
Abstract Background: 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. Methods: 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. Results: 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. Conclusion: These results suggest that LAD1 expression is associated with the metastatic progression of colorectal cancer by promoting the migration and invasion of cancer cells. Keywords: Ladinin-1, Colorectal cancer, Metastasis, Migration, Invasion
Background Colorectal cancer is one of the deadliest cancers, accounting for approximately 10% of cancer-related deaths [1]. While the survival rates of colorectal cancer patients with localized and regional tumors are almost 89 and 79%, respectively, those with distant metastatic tumors are lower than 15%, which leads to the high mortality of * Correspondence: [email protected] 1 Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea 2 Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, South Korea Full list of author information is available at the end of the article
this cancer type [2]. Treatment options for metastatic colorectal cancer are limited. While local therapies such as surgery of metastatic sites or radiofrequency ablation have mitigated the morbidity of patients, in many cases including metastasis with multiple sites in the body, the patients are not eligible for these options and are thus treated with systemic therapy [1]. For the last two decades, extensive efforts to develop bett
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