Open Access

Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression

  • Authors:
    • Simone Polvani
    • Sara Pepe
    • Sara Tempesti
    • Mirko Tarocchi
    • Giada Marroncini
    • Lapo Bencini
    • Elisabetta Ceni
    • Tommaso Mello
    • Lucia Picariello
    • Irene Simeone
    • Cecilia Grappone
    • Gabriele Dragoni
    • Lorenzo Antonuzzo
    • Elisa Giommoni
    • Stefano Milani
    • Andrea Galli
  • View Affiliations

  • Published online on: March 28, 2022     https://doi.org/10.3892/ijo.2022.5345
  • Article Number: 55
  • Copyright: © Polvani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The expression of the nuclear receptor transcription factor (TF) COUP‑TFII is broadly associated with cell differentiation and cancer development, including of pancreatic ductal adenocarcinoma (PDAC), a devastating disease with one of the poorest prognoses among cancers worldwide. Recent studies have started to investigate the pathological and physiological roles of a novel COUP‑TFII isoform (COUP‑TFII_V2) that lacks the DNA‑binding domain. As the role of the canonical COUP‑TFII in PDAC was previously demonstrated, the present study evaluated whether COUP‑TFII_V2 may have a functional role in PDAC. It was demonstrated that COUP‑TFII_V2 naturally occurs in PDAC cells and in primary samples, where its expression is consistent with shorter overall survival and peripheral invasion. Of note, COUP‑TFII_V2, exhibiting nuclear and cytosolic expression, is linked to epithelial to mesenchymal transition (EMT) and cancer progression, as confirmed by nude mouse experiments. The present results demonstrated that COUP‑TFII_V2 distinctively regulates the EMT of PDAC and, similarly to its sibling, it is associated with tumor aggressiveness. The two isoforms have both overlapping and exclusive functions that cooperate with cancer growth and dissemination. By studying how PDAC cells switch from one isoform to the other, novel insight into cancer biology was gained, indicating that this receptor may serve as a novel possible target for PDAC management.
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May-2022
Volume 60 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Polvani S, Pepe S, Tempesti S, Tarocchi M, Marroncini G, Bencini L, Ceni E, Mello T, Picariello L, Simeone I, Simeone I, et al: Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression. Int J Oncol 60: 55, 2022
APA
Polvani, S., Pepe, S., Tempesti, S., Tarocchi, M., Marroncini, G., Bencini, L. ... Galli, A. (2022). Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression. International Journal of Oncology, 60, 55. https://doi.org/10.3892/ijo.2022.5345
MLA
Polvani, S., Pepe, S., Tempesti, S., Tarocchi, M., Marroncini, G., Bencini, L., Ceni, E., Mello, T., Picariello, L., Simeone, I., Grappone, C., Dragoni, G., Antonuzzo, L., Giommoni, E., Milani, S., Galli, A."Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression". International Journal of Oncology 60.5 (2022): 55.
Chicago
Polvani, S., Pepe, S., Tempesti, S., Tarocchi, M., Marroncini, G., Bencini, L., Ceni, E., Mello, T., Picariello, L., Simeone, I., Grappone, C., Dragoni, G., Antonuzzo, L., Giommoni, E., Milani, S., Galli, A."Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression". International Journal of Oncology 60, no. 5 (2022): 55. https://doi.org/10.3892/ijo.2022.5345