2. Academic Validation
  3. Cofilin is a key regulator of oxidative stress-induced intercellular tunneling nanotubes formation

Cofilin is a key regulator of oxidative stress-induced intercellular tunneling nanotubes formation

  • Int J Biochem Cell Biol. 2025 Sep:186:106820. doi: 10.1016/j.biocel.2025.106820.
Hongce Chen 1,  Zhirui Wu 2,  Lingyu Wang 2,  Jingyao Zeng 2,  Tongsheng Chen 3
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510631, China. Electronic address: chenhce@m.scnu.edu.cn.
  • 2 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510631, China.
  • 3 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510631, China. Electronic address: chentsh@scnu.edu.cn.
PMID: 40499810 DOI: 10.1016/j.biocel.2025.106820
Abstract

Tunneling nanotubes (TNTs) are open membranous channels between connected cells, TNTs-mediated substance transfer between tumor cells plays an important role in drug resistance, metastasis and recurrence of tumors. This study aims to explore the composition of TNTs between tumor cells and the function of cofilin in TNTs formation. Oxidative stress induces the formation of TNTs between tumor cells. The components of TNTs include microfilaments and cell membranes, some of which contain microtubules, as well as mitochondria, endoplasmic reticulum, lysosomes, lipid droplets, ions, etc. Förster resonance energy transfer (FRET) analysis of living cells showed that cofilin and actin only interact in TNTs, and inhibition of cofilin can suppress oxidative stress-induced TNTs production. Doxorubicin (DOX) induced senescent tumor cells (STC) can form TNTs, and TNTs mediated material transfer between STC can promote tumor cell survival, while inhibition of cofilin can promote STC death. In summary, our data suggests that cofilin plays an important role in the formation of TNTs, and targeted inhibition of TNTs mediated intercellular communication and material exchange holds significant potential as a novel Cancer treatment strategy.

Keywords

Cofilin; Microfilament; Oxidative stress; Senescent tumor cell; Tunneling nanotubes.

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