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Updated: May 27, 2025

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

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MEK5-ERK5 pathway mediates mitophagy by regulating Nur77 to promote tumorigenesis of osteosarcoma cells

Jianshu Wang1, Jinxu Xue1, Baijing Ma2

  • 1Department of Bone and Soft Tissue Oncology, Gansu Provincial Cancer Hospital, Lanzhou, 730050, China.

European Journal of Medical Research
|February 19, 2025
PubMed
Abstract

Insights

The MEK5-ERK5 pathway regulates mitophagy in osteosarcoma (OS) by controlling Nur77 expression, promoting tumor growth. This pathway presents a potential therapeutic target for OS treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Osteosarcoma (OS) is a primary bone malignancy with poor prognosis.
  • Mitophagy, the selective degradation of damaged mitochondria, plays a role in cancer progression.
  • The MEK5/ERK5 signaling pathway is implicated in various cellular processes, including cancer.

Purpose of the Study:

  • To elucidate the role of the MEK5/ERK5 pathway in mitophagy within osteosarcoma.
  • To identify the molecular mechanisms linking MEK5/ERK5 signaling to mitophagy and OS tumorigenesis.

Main Methods:

  • Differential gene expression analysis and pathway enrichment analysis (GSVA) were performed on OS patient data.
  • Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting assessed protein expression.
  • Cellular assays (CCK-8, Transwell) and mitochondrial potential measurements (JC-1 staining) were utilized.

Main Results:

  • Four mitophagy-related differentially expressed genes were identified, including PINK1.
  • Nur77 expression was significantly higher in metastatic OS and negatively correlated with mitophagy pathways.
  • The MEK5/ERK5 pathway was activated in OS, promoting Nur77 expression, tumorigenesis, and mitochondrial function, while MEK5 downregulation affected mitophagy markers.

Conclusions:

  • The MEK5-ERK5 pathway regulates mitophagy via Nur77, thereby promoting osteosarcoma cell tumorigenesis.
  • Targeting the MEK5-ERK5 pathway and Nur77 offers a promising therapeutic strategy for osteosarcoma.
Keywords:
MEK5–ERK5 pathwayMitophagyNur77Osteosarcoma

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