Anti‑tumor properties of FoxO1 in YD‑9 oral squamous cell carcinoma cells

Yu Gyung Kim, Chaeeun Seong, Kyoung Ah Cho, Sang Min Lee, Tae Jun Kim, Hyeon Ji Kim, Jin Hwa Cho, Won Jung, Sungil Jang, Jae Cheon Shin, Kyung Ha Lee, Jin Seok Byun, Do Yeon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Oral squamous cell carcinoma (OSCC) is a tumor with a poor prognosis and a high recurrence rate. Despite its high annual incidence worldwide, appropriate therapeutic strategies have not yet been developed. Consequently, the 5-year survival rate for OSCC is low when advanced stages or recurrence is diagnosed. Forkhead transcriptional factor O1 (FoxO1) is a key mediator for maintaining cellular homeostasis. FoxO1 can function as a tumor suppressor as well as an oncogene depending on the cancer type. Therefore, the precise molecular functions of FoxO1 need to be validated, considering intracellular factors and the extracellular environment. To the best of our knowledge, however, the roles of FoxO1 in OSCC have not yet been defined. The present study examined FoxO1 levels under pathological conditions (oral lichen planus and oral cancer) and selected an appropriate OSCC cell line (YD-9). Crispr/Cas9 was used to generate FoxO1-deficient YD-9 cells in which the protein levels of phospho ERK and phospho STAT3 were upregulated, promoting cancer proliferation and migration. In addition, FoxO1 reduction increased the levels of the cell proliferation markers phospho H3 (Ser10) and PCNA. FoxO1 loss significantly reduced cellular ROS levels and apoptosis in YD-9 cells. Collectively, the present study demonstrated that FoxO1 exerted an anti-tumor effect by suppressing proliferation and migration/invasion but promoting oxidative stress-linked cell death in YD-9 OSCC cells.

Original languageEnglish
Article number20238559
JournalOncology Reports
Volume49
Issue number6
DOIs
StatePublished - Jun 2023

Keywords

  • forkhead transcriptional factor O1
  • oral squamous cell carcinoma
  • proliferation
  • reactive oxygen species

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