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

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.