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Research article
kangdong liu
Zhengzhou University
Corresponding Author
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Background Esophageal 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. Methods Tissue 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. Results The 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. Conclusion The 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. Keywords esophageal squamous cell carcinoma; TOPK; tumor metastasis; Src/GSK3β/STAT3; γ-catenin
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.
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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
Version 2
Posted 20 Nov, 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
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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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
Version 2
Posted 20 Nov, 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
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 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. Methods Tissue 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. Results The 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. Conclusion The 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. Keywords esophageal squamous cell carcinoma; TOPK; tumor metastasis; Src/GSK3β/STAT3; γ-catenin
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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