PLOD2 contributes to drug resistance in laryngeal cancer by promoting cancer stem cell-like characteristics

Abstract

Background: Advanced stage laryngeal squamous cell carcinoma (LSCC) presents a poor prognosis; thus, there is a great need to identify novel prognostic molecular markers. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is thought to be a novel prognostic factor in several cancers, but its role in LSCC remains unknown. Cancer stem cells (CSCs) are responsible for most instances of tumor recurrence and the development of drug resistance and have been proven to be present in head and neck cancers. Our preliminary study indicated that PLOD2 was elevated in LSCC tissues; therefore, we hypothesized that PLOD2 is related to the prognosis of LSCC patients and aimed to explore the role and underlying mechanism of PLOD2 in LSCC. Methods: We validated the prognostic role of PLOD2 in 114 LSCC patients by immunohistochemistry. Stable PLOD2-overexpressing Hep-2 and FaDu cells were established and assessed by molecular biology and biochemistry methods both in vitro and in vivo. Results: We confirmed that PLOD2 overexpression was correlated with poor prognosis in LSCC patients. PLOD2 overexpression strengthened the CSC-like properties of Hep-2 and FaDu cells, activated the Wnt signaling pathway and conferred drug resistance in LSCC in vitro and in vivo. Conclusions: We found that PLOD2 could serve as a prognostic marker in patients with LSCC and confer drug resistance in LSCC by increasing CSC-like traits; in addition, a Wnt-responsive CSC pathway was identified.