Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer.

INTRODUCTION

The aim of this study was to evaluate the expression of C-type lectin domain family 3 member A (CLEC3A) and its clinical significance in breast invasive ductal cancer (IDC) as well as its effect on breast cancer (BC) cell proliferation and metastasis. In this study, the level of CLEC3A expression in The Cancer Genome Atlas (TCGA) datasets was analyzed.

MATERIALS AND METHODS

Clinical collected samples and BC cells were measured using quantitative reverse transcription polymerase chain reaction. Its correlations with patients' clinicopathological characteristics were analyzed by Pearson's chi-squared test. Overall survival (OS) analysis was performed by the Kaplan-Meier method and Cox's proportional-hazards model. BC cell proliferation, migration, and invasion by CLEC3A knockdown were assessed using Cell Counting Kit-8 and colony formation assay, wound healing model and transwell assay, respectively, in BT474 cell line. Activities of survival factors and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling were measured by testing key molecules using Western blot assay.

RESULTS

CLEC3A expression was markedly higher in breast IDC tissues than normal breast tissues or adjacent normal tissue. Patients with high CLEC3A expression related to higher lymph node and poorer OS of breast IDC. CLEC3A knockdown by siRNA could inhibit the BC cells BT474 proliferation, migration, and invasion, together with a decrease in expression of key proteins in survival factors and PI3K/AKT signaling pathway.

CONCLUSION

Elevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K/AKT signaling activity. These findings unravel that CLEC3A is a promising therapeutic target for BC in the future.