Role of the AMPK/ACC Signaling Pathway in TRPP2‐Mediated Head and Neck Cancer Cell Proliferation

Abstract

Transient receptor potential polycystic 2 (TRPP2) exerts vital roles in various types of cancer; however, its underlying mechanisms remain largely unknown. This study is aimed at investigating whether knockdown of TRPP2 affected the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling pathway and the proliferation of HN-4, cell line originating from human oral and hypopharyngeal squamous cell carcinoma. In addition, the interactions among AMPK/ACC, AMPK/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2<i>α</i> (eIF2<i>α</i>) and TRPP2/PERK/eIF2<i>α</i> signaling pathways, and their association with cell proliferation were also explored. The results showed that the relative expression levels of phosphorylated (p)-ACC, p-PERK, and p-eIF2<i>α</i> in HN-4 cells were significantly increased following treatment with 5-aminoimidazole-4-carboxamide-1-<i>β</i>-D-ribofuranoside (AICAR) and significantly decreased in cells treated with compound C. Therefore, consistent with previous studies, the AMPK/ACC and AMPK/PERK/eIF2<i>α</i> signaling pathways were upregulated and downregulated following treatment with an AMPK agonist and inhibitor, respectively. Furthermore, TRPP2 knockdown decreased p-PERK and p-eIF2<i>α</i> expression levels and increased those of p-AMPK and p-ACC. Additionally, knockdown of TRPP2 increased HN-4 cell proliferation, while treatment with an AMPK inhibitor or agonist increased or inhibited TRPP2-specific siRNA-mediated cell proliferation, respectively. In conclusion, silencing of TRPP2 expression increased HN-4 cell proliferation via inhibiting the PERK/eIF2<i>α</i> signaling pathway, while the AMPK/ACC signaling pathway was possibly activated by a feedback mechanism to reduce enhanced cell proliferation.