PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating Epithelial-Mesenchymal Transition

Abstract Objective Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis (LM). This research aimed to determine the PKM2 role in LM in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Kaplan-Meier and COX's regression analysis were employed to determine PKM2's prognostic value, while western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo . After that, Transwell assay, Wound Healing assay, Flow cytometry, EdU, and an in vivo Popliteal lymphatic metastasis mice model were employed to show the role of PKM2 in FaDu cell lines. In vitro and in viv o studies also confirmed lymphatic metastasis's mechanism. Results Prominent PKM2 overexpression was seen in patients with LM of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition (EMT), but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and LM. Conclusions Our findings suggest that PKM2 may be a tumor's promoter gene of LM, which may promote LM of HPC by regulating EMT. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.