HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

Dong, Jing; Zhang, Xueyuan; Du, Xuehui; Zou, Naiyi; Shen, Wenbin; Ma, Ming; Wang, Yaojie; Zhu, Shuchai

doi:10.7150/jca.73761

Cited by 5 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and promote aggressive phenotypes and radioresistance of ESCC cells (18,19). However, the impacts of HMGB1 on oxidative phosphorylation in ESCC and the relationship between PTMA and HMGB1 have not been covered.…”

Section: What Are the Implications And What Should Change Now?mentioning

confidence: 99%

“…High mobility group box 1 ( HMGB1 ) is a highly conserved nucleoprotein that has been uncovered to play a role in the pathogenesis of inflammatory diseases and malignant tumors ( 16 , 17 ). Further, HMGB1 overexpression has been reported to be associated with poorer overall survival rate and progression-free survival of ESCC patients and promote aggressive phenotypes and radioresistance of ESCC cells ( 18 , 19 ). However, the impacts of HMGB1 on oxidative phosphorylation in ESCC and the relationship between PTMA and HMGB1 have not been covered.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma

Chen¹,

He²,

Lin³

et al. 2023

J Thorac Dis

View full text Add to dashboard Cite

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with complex pathogenesis. There is a pressing need to search for ESCC targeted therapy sites and explore its pathogenesis. Prothymosin alpha (PTMA) is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of PTMA in ESCC have not yet been reported. Methods: We first detected the PTMA expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, PTMA expression in ESCC cells was inhibited by cell transfection, and cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and Western blot. A dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect reactive oxygen species (ROS) level in cells, and MitoSOX fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining, mitochondrial complex kit, and Western blot were used to detect the expression of mitochondrial oxidative phosphorylation. Next, the combination between PTMA and high mobility group box 1 (HMGB1) was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of PTMA was inhibited and the expression of HMGB1 was overexpressed in cells via cell transfection, and the regulatory effect of PTMA and HMGB1 binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments. Results: The expression of PTMA in ESCC was abnormally elevated. The inhibition of PTMA expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with PTMA can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to HMGB1. Conclusions: PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.

show abstract

Section: What Are the Implications And What Should Change Now?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma

Chen¹,

He²,

Lin³

et al. 2023

J Thorac Dis

View full text Add to dashboard Cite

show abstract

“…The effects observed in vivo are remarkably diverse—metabolic changes, epithelial to mesenchymal transition (EMT), stimulation of autophagy, enhancement of immune suppression, local invasion, angiogenesis, metastasis, radio-resistance, and chemoresistance. These protumoral effects are probably due a direct impact of HMGB1 on malignant cells and to indirect mechanisms involved in inflammatory processes [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Biology Of Tumor Necrosis and Extra-cellular Necrotic Productsmentioning

confidence: 99%

Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth

Zapletal

Vasiljevic

Busson

et al. 2023

IJMS

View full text Add to dashboard Cite

Damage-associated molecular patterns (DAMPs) are endogenous molecules released from the necrotic cells dying after exposure to various stressors. After binding to their receptors, they can stimulate various signaling pathways in target cells. DAMPs are especially abundant in the microenvironment of malignant tumors and are suspected to influence the behavior of malignant and stromal cells in multiple ways often resulting in promotion of cell proliferation, migration, invasion, and metastasis, as well as increased immune evasion. This review will start with a reminder of the main features of cell necrosis, which will be compared to other forms of cell death. Then we will summarize the various methods used to assess tumor necrosis in clinical practice including medical imaging, histopathological examination, and/or biological assays. We will also consider the importance of necrosis as a prognostic factor. Then the focus will be on the DAMPs and their role in the tumor microenvironment (TME). We will address not only their interactions with the malignant cells, frequently leading to cancer progression, but also with the immune cells and their contribution to immunosuppression. Finally, we will emphasize the role of DAMPs released by necrotic cells in the activation of Toll-like receptors (TLRs) and the possible contributions of TLRs to tumor development. This last point is very important for the future of cancer therapeutics since there are attempts to use TLR artificial ligands for cancer therapeutics.

show abstract