PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression

R. Uchi, R. Kogo, K. Kawahara, T. Sudo, T. Yokobori, H. Eguchi, K. Sugimachi, T. Maehama, M. Mori, A. Suzuki, S. Komune, K. Mimori

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Abstract

Background:The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.Methods:To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.Results:Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).Conclusion:The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.

Original languageEnglish
Pages (from-to)2199-2206
Number of pages8
JournalBritish journal of cancer
Volume109
Issue number8
DOIs
Publication statusPublished - Oct 15 2013

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Stomach Neoplasms
Neoplasms
Ribosomal Proteins
Cell Cycle Checkpoints
Small Interfering RNA
Cell Proliferation
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression. / Uchi, R.; Kogo, R.; Kawahara, K.; Sudo, T.; Yokobori, T.; Eguchi, H.; Sugimachi, K.; Maehama, T.; Mori, M.; Suzuki, A.; Komune, S.; Mimori, K.

In: British journal of cancer, Vol. 109, No. 8, 15.10.2013, p. 2199-2206.

Research output: Contribution to journalArticle

Uchi, R, Kogo, R, Kawahara, K, Sudo, T, Yokobori, T, Eguchi, H, Sugimachi, K, Maehama, T, Mori, M, Suzuki, A, Komune, S & Mimori, K 2013, 'PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression', British journal of cancer, vol. 109, no. 8, pp. 2199-2206. https://doi.org/10.1038/bjc.2013.561
Uchi R, Kogo R, Kawahara K, Sudo T, Yokobori T, Eguchi H et al. PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression. British journal of cancer. 2013 Oct 15;109(8):2199-2206. https://doi.org/10.1038/bjc.2013.561
Uchi, R. ; Kogo, R. ; Kawahara, K. ; Sudo, T. ; Yokobori, T. ; Eguchi, H. ; Sugimachi, K. ; Maehama, T. ; Mori, M. ; Suzuki, A. ; Komune, S. ; Mimori, K. / PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression. In: British journal of cancer. 2013 ; Vol. 109, No. 8. pp. 2199-2206.
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