See the published version of this article at Journal of Experimental & Clinical Cancer Research.
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
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Qingyong Ma
Xi'an Jiaotong University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Experimental & Clinical Cancer Research.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.
Methods: The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR).
Results: In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.
Conclusion: Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
Keywords
pancreatic ductal adenocarcinoma, heat shock factor 1, epidermal growth factor receptor, transgenic mice, tumorigenesis
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.docx
Additional file 1: Figure S1: Related technologies mentioned in this article and basic morphology/pathology features of KC mice. Figure S2: Pharmacological inhibition of HSF1 suppressed the formation of ADM in vitro. Figure S3: EGFR stimulation activated HSF1 doubly in pancreatic acinar cells.
- Additionalfile2.xlsx
Additional file 2: Table S1: Source files of bioinformatics analysis on HSF1 and its related proteins (mainly TCGA PAAD datasets).
- Additionalfile3.xlsx
Additional file 3: Table S2: Source files of bioinformatics analysis on EGFR (mainly TCGA PAAD datasets).
- Additionalfile4.xlsx
Additional file 4: Table S3: Source files of bioinformatics analysis on EGFR pathway (GEO GSE98399 datasets).
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
Version 2
Posted 31 Dec, 2020
Published
On 09 Jan, 2021
No community comments so far
Editorial decision: Accept
On 24 Dec, 2020
Review #2 received
Received 23 Dec, 2020
Reviewer #2 agreed
On 20 Dec, 2020
Reviewer #1 agreed
On 15 Dec, 2020
Review #1 received
Received 15 Dec, 2020
Editor assigned
On 14 Dec, 2020
Reviewers invited
Invitations sent on 14 Dec, 2020
Submission checks complete
On 14 Dec, 2020
Editor invited
On 14 Dec, 2020
No comments provided
Editorial decision: Major revision
On 09 Oct, 2020
Review #2 received
Received 02 Oct, 2020
Reviewer #3 agreed
On 21 Sep, 2020
Reviewer #2 agreed
On 31 Aug, 2020
Review #1 received
Received 25 Aug, 2020
Reviewer #1 agreed
On 14 Aug, 2020
Editor assigned
On 07 Aug, 2020
Reviewers invited
Invitations sent on 07 Aug, 2020
First submitted
On 06 Aug, 2020
Submission checks complete
On 06 Aug, 2020
Editor invited
On 06 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at Journal of Experimental & Clinical Cancer Research. A preprint is 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
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Qingyong Ma
Xi'an Jiaotong 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
Version 2
Posted 31 Dec, 2020
Published
On 09 Jan, 2021
No community comments so far
Editorial decision: Accept
On 24 Dec, 2020
Review #2 received
Received 23 Dec, 2020
Reviewer #2 agreed
On 20 Dec, 2020
Reviewer #1 agreed
On 15 Dec, 2020
Review #1 received
Received 15 Dec, 2020
Editor assigned
On 14 Dec, 2020
Reviewers invited
Invitations sent on 14 Dec, 2020
Submission checks complete
On 14 Dec, 2020
Editor invited
On 14 Dec, 2020
No comments provided
Editorial decision: Major revision
On 09 Oct, 2020
Review #2 received
Received 02 Oct, 2020
Reviewer #3 agreed
On 21 Sep, 2020
Reviewer #2 agreed
On 31 Aug, 2020
Review #1 received
Received 25 Aug, 2020
Reviewer #1 agreed
On 14 Aug, 2020
Editor assigned
On 07 Aug, 2020
Reviewers invited
Invitations sent on 07 Aug, 2020
First submitted
On 06 Aug, 2020
Submission checks complete
On 06 Aug, 2020
Editor invited
On 06 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Experimental & Clinical Cancer Research.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.
Methods: The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR).
Results: In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.
Conclusion: Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6