High Mobility Group Box 1 Promotes Lung Cancer Cell Migration and Motility via Regulation of Dynamin-Related Protein 1

Abstract

High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.

Role of Extracellular High-Mobility Group Box-1 as a Therapeutic Target of Gastric Cancer

“…Intracellular and extracellular HMGB1 have both been reported to contribute to carcinogenesis, cancer progression, and metastasis [ 21 , 25 , 37 , 38 ]. We herein examined the effects of the down-regulation of intracellular HMGB1 using siRNA on cell functions and found that cell proliferation, migration, and invasion abilities were reduced in GC cells, which is consistent with previous findings [ 39 ] ( Figure S2 ).…”

Puerarin Alleviates LPS-Induced H9C2 Cell Injury by Inducing Mitochondrial Autophagy

“…32,33 Drp1 is often upregulated during mitochondrial fission, whereas MFN1 is downregulated during that process. 34,35 Yang et al 36 found that the squamosamide derivative FLZ could inhibit mitochondrial fission via downregulation of Drp1; Liu et al 37 reported that HMGB1 could inhibit mitochondrial fission in lung cancer cells via mediation of Drp1 and MFN1. Our findings were in line with those previous reports, by suggesting that Puerarin could reverse LPS-induced mitochondrial fission in H9C2 cells by regulating Drp1 and MFN1.…”

Investigating the Effects of HMGB1 Overexpression on Colorectal Cancer Cell Migration via Oncolytic Herpes simplex Virus Type 1 (oHSV-1)

“…Recent research has also implicated HMGB1 in cancer progression, particularly in the context of promoting cancer cell migration. Several studies have reported that HMGB1 can act as a potent inducer of cancer cell migration, facilitating the dissemination of cancer cells from primary tumor sites to distant locations within the body [16][17][18] . This pro-migratory effect of HMGB1 has raised significant interest in understanding its role in cancer metastasis and its potential implications for therapeutic interventions.…”