CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α

Wu, Xianxian; Zhang, Hongdian; Sui, Zhilin; Gao, Yongyin; Gong, Lei; Chen, Chuangui; Ma, Zhao; Tang, Peng; Yu, Zhentao

doi:10.1111/cas.15265

Cited by 10 publications

(6 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The wound-healing assay was conducted to evaluate cellular migration according to our published protocol [ 17 ]. ESCC cells were seeded into 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC. Methods Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT–PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively. Results The expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P < 0.05). High PPFIA1 expression was closely related to several clinicopathological characteristics, including tumor location, histological grade, tumor invasion depth, lymph node metastasis, and tumor-node-metastasis (TNM) stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic factor of overall survival in ESCC patients (GSE53625 dataset, P = 0.019; cDNA array dataset, P < 0.001; TMA dataset, P = 0.039). Downregulation of PPFIA1 expression can significantly reduce the migration and invasion ability of ESCC cells. Conclusion PPFIA1 is related to the migration and invasion of ESCC cells, and can be used as a potential biomarker to evaluate the prognosis of ESCC patients.

show abstract

“…The wound-healing assay was conducted to evaluate cellular migration according to our published protocol [ 17 ]. ESCC cells were seeded into 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Colony formation and CCK-8 assays were conducted according to our published protocol [16]. The EdU assay was performed using a Click-iT EdU Kit (BeyoClick™ EdU-555).…”

Section: Western Blottingmentioning

confidence: 99%

“…Cell migration assessment was performed following the above steps, except that the top chambers were not coated with Matrigel. Metastasis experiments were performed as previously described [16]. ESCC cells (5 × 10 5 ) labeled with luciferase were injected into male SCID/ Beige mice via the tail vein.…”

Section: Transwell Assaymentioning

confidence: 99%

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1

Zhang,

Han,

Xiao

et al. 2023

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-β-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

show abstract

“…Similar to other solid tumors, hypoxia is closely linked to the development, advancement, spread, blood vessel formation, the transition of cells from epithelial to mesenchymal (EMT), and sensitivity to radiation of Esophageal Squamous Cell Carcinoma (ESCC) [ 22 ]. Hypoxia-inducible factor-1α (HIF-1α) is known to govern the response of cells to hypoxia and has been found to be highly active in ESCC, leading to a poor prognosis, spread, invasion, and resistance to therapy [ 23 – 26 ]. In low-oxygen conditions, HIF-1 connects to the hypoxia response element (HRE) and triggers specific genes, including Snail, Slug, and Pol ι [ 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

DNA polymerase iota promotes EMT and metastasis of esophageal squamous cell carcinoma by interacting with USP7 to stabilize HIF-1α

Gao,

Zhang,

Zhu

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer types, with a low 5-year survival rate of ~20%. Our prior research has suggested that DNA Polymerase iota (Pol ι), a member of Y-family DNA polymerase, plays a crucial role in the invasion and metastasis of ESCC. However, the underlying mechanism is not well understood. In this study, we utilized ChIP-PCR and luciferase reporter assays to investigate the binding of HIF-1α to the promoter of the Pol ι gene. Transwell, wound healing, and mouse models were employed to assess the impact of Pol ι and HIF-1α on the motility of ESCC cells. Co-immunoprecipitation and Western blot were carried out to explore the interaction between Pol ι and HIF-1α, while qRT-PCR and Western blot were conducted to confirm the regulation of Pol ι and HIF-1α on their downstream targets. Our results demonstrate that HIF-1α activates the transcription of the Pol ι gene in ESCC cells under hypoxic conditions. Furthermore, the knockdown of Pol ι impeded HIF-1α-induced invasion and metastasis. Additionally, we found that Pol ι regulates the expression of genes involved in epithelial-mesenchymal transition (EMT) and initiates EMT through the stabilization of HIF-1α. Mechanistically, Pol ι maintains the protein stability of HIF-1α by recruiting USP7 to mediate the deubiquitination of HIF-1α, with the residues 446–578 of Pol being crucial for the interaction between Pol ι and USP7. Collectively, our findings unveil a novel feedforward molecular axis of HIF-1α- Pol ι -USP7 in ESCC that contributes to ESCC metastasis. Hence, our results present an attractive target for intervention in ESCC.

show abstract

CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α

Cited by 10 publications

References 38 publications

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1

DNA polymerase iota promotes EMT and metastasis of esophageal squamous cell carcinoma by interacting with USP7 to stabilize HIF-1α

Contact Info

Product

Resources

About