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

被引：10

作者：

Liu, Wei-Lun ^{[1
,2
]}

Li, Chia-Yang ^{[3
,4
]}

Cheng, Wei-Chung ^{[5
]}

Chang, Chia-Yuan ^{[6
]}

Chen, Yung-Hsiang ^{[7
,8
]}

Lu, Chi-Yu ^{[9
]}

Wang, Shu-Chi ^{[4
,10
,11
]}

Liu, Yu-Ru ^{[12
]}

Cheng, Meng-Hsuan ^{[12
,13
,14
]}

Chong, Inn-Wen ^{[12
]}

Liu, Po-Len ^{[4
,12
,15
]}

机构：

[1] Fu Jen Catholic Univ, Sch Med, Coll Med, New Taipei 242, Taiwan

[2] Fu Jen Catholic Univ, Fu Jen Catholic Univ Hosp, Div Crit Care Med, Dept Emergency & Crit Care Med, New Taipei 243, Taiwan

[3] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung 807, Taiwan

[4] Kaohsiung Med Univ, Ctr Canc Res, Kaohsiung 807, Taiwan

[5] China Med Univ, Grad Inst Biomed Sci, Res Ctr Canc Biol, Taichung 404, Taiwan

[6] Natl Cheng Kung Univ, Dept Mech Engn, Tainan 701, Taiwan

[7] China Med Univ, Grad Inst Integrated Med, Coll Chinese Med, Taichung 404, Taiwan

[8] Asia Univ, Dept Psychol, Coll Med & Hlth Sci, Taichung 413, Taiwan

[9] Kaohsiung Med Univ, Dept Biochem, Coll Med, Kaohsiung 807, Taiwan

[10] Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung 807, Taiwan

[11] Kaohsiung Med Univ, Ctr Liquid Biopsy, Kaohsiung 807, Taiwan

[12] Kaohsiung Med Univ, Dept Resp Therapy, Coll Med, Kaohsiung 807, Taiwan

[13] Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Dept Internal Med, Kaohsiung 807, Taiwan

[14] Kaohsiung Med Univ, Sch Med, Coll Med, Kaohsiung 807, Taiwan

[15] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 07期

关键词：

non-small cell lung cancer; high mobility group box 1; dynamin related protein 1; cytoskeleton dynamics; lamellipodia; filopodia; mitochondrial fission; HMGB1; PHOSPHORYLATION; MICROTUBULES; METASTASIS; EXPRESSION; FILOPODIA; INVASION; FISSION; ACTIN;

D O I：

10.3390/ijms22073628

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：17

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