Lymphocyte Antigen 6 Family Member D (LY6D) Affects Stem Cell Phenotype and Progression of Pancreatic Adenocarcinoma.

Abstract

The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC. We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC. In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC. Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.