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E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma

Bertonnier-Brouty, Ludivine LU ; Andersson, Jonas LU ; Kaprio, Tuomas ; Hagström, Jaana ; Bsharat, Sara LU ; Asplund, Olof LU ; Hatem, Gad LU ; Haglund, Caj ; Seppänen, Hanna and Prasad, Rashmi B LU , et al. (2024) In Cancer Medicine 13(9).
Abstract

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs.

OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion.

METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1... (More)

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs.

OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion.

METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells.

CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Carcinoma, Pancreatic Ductal/genetics, Pancreatic Neoplasms/genetics, Cell Proliferation, E2F1 Transcription Factor/metabolism, Cell Line, Tumor, Cell Movement/genetics, Apoptosis, Gene Expression Regulation, Neoplastic, Animals, Repressor Proteins/genetics, Cell Survival/genetics, Mice
in
Cancer Medicine
volume
13
issue
9
article number
e7187
pages
18 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:38686617
  • scopus:85191748139
ISSN
2045-7634
DOI
10.1002/cam4.7187
language
English
LU publication?
yes
id
13628177-dd32-46d5-9a5c-6e994a820755
date added to LUP
2024-05-07 09:12:01
date last changed
2024-05-22 05:56:39
@article{13628177-dd32-46d5-9a5c-6e994a820755,
  abstract     = {{<p>BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs.</p><p>OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion.</p><p>METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells.</p><p>CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.</p>}},
  author       = {{Bertonnier-Brouty, Ludivine and Andersson, Jonas and Kaprio, Tuomas and Hagström, Jaana and Bsharat, Sara and Asplund, Olof and Hatem, Gad and Haglund, Caj and Seppänen, Hanna and Prasad, Rashmi B and Artner, Isabella}},
  issn         = {{2045-7634}},
  keywords     = {{Humans; Carcinoma, Pancreatic Ductal/genetics; Pancreatic Neoplasms/genetics; Cell Proliferation; E2F1 Transcription Factor/metabolism; Cell Line, Tumor; Cell Movement/genetics; Apoptosis; Gene Expression Regulation, Neoplastic; Animals; Repressor Proteins/genetics; Cell Survival/genetics; Mice}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cancer Medicine}},
  title        = {{E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma}},
  url          = {{http://dx.doi.org/10.1002/cam4.7187}},
  doi          = {{10.1002/cam4.7187}},
  volume       = {{13}},
  year         = {{2024}},
}