Journal
BRITISH JOURNAL OF CANCER
Volume 109, Issue 8, Pages 2199-2206Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2013.561
Keywords
PICT1; TP53; gastric cancer; RPL11; MDM2; GLTSCR2
Categories
Funding
- CREST
- Japan Science and Technology Agency (JST)
- Japan Society for the Promotion of Science (JSPS)
- Funding Program for Next Generation World-Leading Researchers [LS094]
- NEDO (New Energy and Industrial Technology Development Organization)
- [20390360]
- [20591547]
- [20790960]
- [21591644]
- [21791295]
- [21791297]
- [215921014]
- [21679006]
- Grants-in-Aid for Scientific Research [23592132] Funding Source: KAKEN
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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.
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