Biological Sciences Division
Published May 25, 2023 | Version v1
Journal article Open

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma

Creators

  • 1. University of Chicago
  • 2. University of Tokyo
  • 3. Anicom Specialty Medical Institute Inc.
  • 4. Japan Small Animal Cancer Center
  • 5. Shikoku Veterinary Medical Center
  • 6. Nippon Veterinary and Life Science University

Description

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Data availability

All data generated or analyzed during this study except for those generated by WES and RNA-seq are included in this published article. Datasets obtained through WES and RNA-seq analyses are available at the DDBJ Sequenced Read Archive repository with accession number DRA010452 (https://ddbj.nig.ac.jp/resource/sra-submission/DRA010452), DRA013421 (https://ddbj.nig.ac.jp/resource/sra-submission/DRA013421) and DRA013450 (https://ddbj.nig.ac.jp/resource/sra-submission/DRA013450).

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Additional details

Identifiers

DOI
10.1038/s41598-023-35813-1
Other
oai:uchicago.tind.io:9827

Funding

Japan Society for the Promotion of Science
17H05043
Japan Society for the Promotion of Science
17H03921

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Obstetrics and Gynecology