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Research article
kangdong liu
Zhengzhou University
Corresponding Author
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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.
Keywords
Esophageal squamous cell carcinoma, TOPK, Tumor metastasis, Src/GSK3β/STAT3, γ-catenin
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CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 11 Dec, 2019
Editor assigned
On 10 Dec, 2019
Editor invited
On 09 Dec, 2019
Submission checks complete
On 08 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 06 Dec, 2019
Review #2 received
Received 05 Dec, 2019
Reviewer #2 agreed
On 17 Nov, 2019
Reviewer #1 agreed
On 15 Nov, 2019
Review #1 received
Received 15 Nov, 2019
Reviewers invited
Invitations sent on 14 Nov, 2019
Submission checks complete
On 11 Nov, 2019
Editor invited
On 11 Nov, 2019
Editor assigned
On 11 Nov, 2019
Version 1
Posted 19 Aug, 2019
No comments provided
Editorial decision: Major revision
On 09 Oct, 2019
Review #1 received
Received 30 Sep, 2019
Review #3 received
Received 06 Sep, 2019
Review #2 received
Received 06 Sep, 2019
Reviewer #2 agreed
On 05 Sep, 2019
Reviewer #3 agreed
On 05 Sep, 2019
Reviewers invited
Invitations sent on 04 Sep, 2019
Reviewer #1 agreed
On 04 Sep, 2019
Editor assigned
On 25 Aug, 2019
Submission checks complete
On 24 Aug, 2019
Editor invited
On 13 Aug, 2019
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Subject Areas
Oncology
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A new preprint design is coming!
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See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
kangdong liu
Zhengzhou University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 11 Dec, 2019
Editor assigned
On 10 Dec, 2019
Editor invited
On 09 Dec, 2019
Submission checks complete
On 08 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 06 Dec, 2019
Review #2 received
Received 05 Dec, 2019
Reviewer #2 agreed
On 17 Nov, 2019
Reviewer #1 agreed
On 15 Nov, 2019
Review #1 received
Received 15 Nov, 2019
Reviewers invited
Invitations sent on 14 Nov, 2019
Submission checks complete
On 11 Nov, 2019
Editor invited
On 11 Nov, 2019
Editor assigned
On 11 Nov, 2019
Version 1
Posted 19 Aug, 2019
No comments provided
Editorial decision: Major revision
On 09 Oct, 2019
Review #1 received
Received 30 Sep, 2019
Review #3 received
Received 06 Sep, 2019
Review #2 received
Received 06 Sep, 2019
Reviewer #2 agreed
On 05 Sep, 2019
Reviewer #3 agreed
On 05 Sep, 2019
Reviewers invited
Invitations sent on 04 Sep, 2019
Reviewer #1 agreed
On 04 Sep, 2019
Editor assigned
On 25 Aug, 2019
Submission checks complete
On 24 Aug, 2019
Editor invited
On 13 Aug, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Oncology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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