LAD1 expression is associated with the metastatic potential of colorectal cancer cells

Byul Moon,Eun-Jeong Jeong,Kyu Sang Song,Young Il Yeom,Mijin Park,Jang-Seong Kim,Suk-Jin Yang,Sang-Hyun Lee,Seong Min Park,Jung-Ae Kim

doi:10.1186/s12885-020-07660-0

Abstract

BackgroundAnchoring 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.MethodsWe 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.ResultsWe 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.ConclusionThese results suggest that LAD1 expression is associated with the metastatic progression of colorectal cancer by promoting the migration and invasion of cancer cells.

Highlights

Anchoring filament protein ladinin-1 (LAD1) was related to the aggressive progression of breast, lung, laryngeal and thyroid cancers
Expression of LAD1 transcript correlates with poor prognosis of colorectal cancer To determine the clinical relevance of LAD1 to colorectal cancer, we assessed the correlation of LAD1 mRNA levels with the clinical outcome of colorectal cancer patients
Gene Ontology analyses revealed that biological processes involved in cell morphology and motility, such as cell-cell adhesion and regulation of cell migration, were significantly correlated with LAD1 expression (Fig. 1b)

Summary

Introduction

Anchoring filament protein ladinin-1 (LAD1) was related to the aggressive progression of breast, lung, laryngeal and thyroid cancers. A study of mouse thyroid cancer models revealed a molecular link between LAD1 expression and oncogenic signaling pathways in cancer by showing that the BRAFV600E mutation induced the expression of LAD1 transcripts [10]. Compared with normal tissues, the expression of the LAD1 transcript was elevated in human thyroid cancers carrying oncogenic mutations in genes such as BRAF, RET and RAS [10]. This finding suggests that different oncogenic signaling pathways upregulate LAD1 expression. Studies assessing the involvement of LAD1 in colorectal cancer progression are lacking

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