Genomic lesions drive the metastasis of esophageal squamous cell carcinoma

Lin, De–Chen; Koeffler, H. Phillip

doi:10.21037/jtd.2017.09.58

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…Clinically, tumor metastasis is mostly incurable and is the primary cause of cancer-related morbidity and mortality. Over 50% of ESCC-associated deaths are caused by distal metastasis, which is associated with poor prognosis, to the lymph nodes, lung, liver, bones, adrenal glands, and brain [15]. Therefore, identification of critical regulators that drive invasion and metastasis in ESCC will facilitate the development of new treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin

et al. 2019

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BackgroundEsophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear.MethodsTissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings.ResultsThe enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin.ConclusionThe findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.

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Section: Discussionmentioning

confidence: 99%

TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin

et al. 2019

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“…Over 50% of ESCC-associated deaths are caused by distal metastasis which is associated with poor prognosis and to the lymph nodes, lung, liver, bones, adrenal glands, and brain (15). Therefore, identification of critical regulators and signaling pathways that drive invasion and metastasis in ESCC will facilitate development of new treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

TOPK Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Activating Src/GSK3β/STAT3 Signal Pathway though γ-catenin

Jiang

Zhang

Zhao

et al. 2019

Preprint

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Background Esophageal squamous cell carcinoma (ESCC) is a deadly disease with the poor prognosis in the world. The distal metastasis is the most death reason of ESCC. It is needed to have a comprehensive understanding of the molecular mechanism of metastasis to increase the free survive rate. T-LAK cell-originated protein kinase (TOPK) which is a MAPKK-like kinase takes an vital role in many physical and pathophysiological progress. However, the function of TOPK in ESCC metastasis was unclear. Methods Tissue array was used to evaluate the relationship between TOPK and ESCC patient with lymph node metastasis. Wound healing assay, transwell assay and lung metastasis mice model were assessed for the role of TOPK in the migration of ESCC cells in vitro and in vivo respectively. Protein kinase array, MS and molecular modeling were carried out to find the relational pathways and target protein of TOPK. Even, immune-fluorescence and western blot were performed to evaluate the mechanism of TOPK. Results We found that the high level of TOPK was correlated with the aggressive phenotype in ESCC tissues. Knocking down TOPK inhibited the invasion and migration of ESCC cells. We also verified that TOPK inhibitor HI-TOPK-032 inhibited the lung metastasis in ESCC cell exnograft model. Even more, molecular investigation indicated that TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway by binding with γ-catenin. Conclusion These findings reveal that TOPK was sincerely related with ESCC cell metastasis and TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway. This means that TOPK may be a potential molecular target for ESCC in clinic.

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“…Given that metastasis mainly accounted for poor clinical ESCC outcomes [28], we next investigated if UGT2B15 signaling played a role in the metastasis of ESCC cells. To gain more insights into the function of UGT2B15 in regulating ESCC cell invasion, we established KYSE410 and ZEC014 cells stably overexpressing UGT2B15 and assessed how UGT2B15 influenced the cellular phenotypes in vitro and in vivo.…”

Section: Ugt2b15 Promotes Metastasis In Esccmentioning

confidence: 99%

Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion

Cai,

Huang,

Gao

et al. 2023

Cancers

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Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy with poor prognosis. Interestingly, ESCC is strongly characterized by a male-predominant propensity. Our previous study showed that androgen receptor (AR) orchestrated a transcriptional repression program to promote ESCC growth, but it remains unclear whether AR can also activate oncogenic signaling during ESCC progression. In this study, by analyzing our previous AR cistromes and androgen-regulated transcriptomes, we identified uridine diphosphate glucuronosyltransferase family 2 member B15 (UGT2B15) as a bona fide target gene of AR. Mechanistically, AP-1 cofactors played important and collaborative roles in AR-mediated UGT2B15 upregulation. Functional studies have revealed that UGT2B15 promoted invasiveness in vitro and lymph node metastasis in vivo. UGT2B15 was partially responsible for the AR-induced invasive phenotype in ESCC cells. Importantly, simultaneous blocking of AP-1 and AR resulted in stronger inhibition of cell invasiveness compared to inhibiting AP-1 or AR alone. In conclusion, our study reveals the molecular mechanisms underlying the AR-driven ESCC invasion and suggests that the AR/AP1/UGT2B15 transcriptional axis can be potentially targeted in suppressing metastasis in male ESCC patients.

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Genomic lesions drive the metastasis of esophageal squamous cell carcinoma

Abstract: Comment on: Dai W, Ko JMY, Choi SSA, et al. Whole-exome sequencing reveals critical genes underlying metastasis in oesophageal squamous cell carcinoma.

Cited by 3 publications

References 16 publications

TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin

TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin

TOPK Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Activating Src/GSK3β/STAT3 Signal Pathway though γ-catenin

Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion

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