C4orf47 contributes to the dormancy of pancreatic cancer under hypoxic conditions.

dormancy hypoxia pancreatic cancer

Journal

Journal of Cancer
ISSN: 1837-9664
Titre abrégé: J Cancer
Pays: Australia
ID NLM: 101535920

Informations de publication

Date de publication:
2023
Historique:
received: 16 09 2022
accepted: 12 12 2022
entrez: 6 2 2023
pubmed: 7 2 2023
medline: 7 2 2023
Statut: epublish

Résumé

In our comprehensive analysis of pancreatic cancer pathology, we found that the C4orf47 molecule was upregulated in hypoxic environments. C4orf47 is reported to be a centrosome-associated protein, but its biological significance in cancer is completely unknown; therefore, we assessed its role in pancreatic cancer. We found that C4orf47 was a direct target of HIF-1α and is upregulated in hypoxic conditions, in which it suppressed the cell cycle and inhibits cell proliferation through up-regulation of the cell cycle repressors Fbxw-7, P27, and p57; and the down-regulation of the cell cycle promoters c-myc, cyclinD1, and cyclinC. Furthermore, C4orf47 induced epithelial-mesenchymal transition and enhanced their cell plasticity and invasiveness. In addition, the p-Erk/p-p38 ratio was significantly enhanced and down-regulated CD44 expression by C4orf47 suppression, suggesting that C4orf47 is involved in pancreatic cancer dormancy under hypoxic conditions. Furthermore, the potential of C4orf47 expression was a good prognostic biomarker for pancreatic cancer. These results contribute to the elucidation of the pathology of refractory pancreatic cancer and the development of novel therapeutic strategies.

Identifiants

pubmed: 36741255
doi: 10.7150/jca.78993
pii: jcav14p0306
pmc: PMC9891878
doi:

Types de publication

Journal Article

Langues

eng

Pagination

306-317

Informations de copyright

© The author(s).

Déclaration de conflit d'intérêts

Competing Interests: The authors have declared that no competing interest exists.

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Auteurs

Shinjiro Nagao (S)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Hideya Onishi (H)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Makoto Kawamoto (M)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Shogo Masuda (S)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Lin Na (L)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Shinji Morisaki (S)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Naoya Iwamoto (N)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Yutaka Yamada (Y)

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Satoko Koga (S)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Shu Ichimiya (S)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Kazunori Nakayama (K)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Akira Imaizumi (A)

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Kinichi Nakashima (K)

Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Yoshinao Oda (Y)

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Masafumi Nakamura (M)

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Classifications MeSH