日本研究人员日前发表论文说，他们发现人体细胞核内一种蛋白质是阻碍肌体抑制癌症的“路障”，如果能减少这种蛋白质的量或减少其表达，癌症发展就能得到一定程度的抑制。
九州大学教授铃木聪领导的科研小组在最新一期《自然—医学》（Nature Medicine）杂志网络版上发表论文说，他们研究了人体细胞核内的蛋白质“PICT1”，发现如果这种蛋白质的量减少或表达被抑制，另一种已知具有抑制癌症作用的蛋白质“p53”的量就会显著增加。
研究人员针对癌症患者进行的病变组织分析显示，“PICT1”蛋白质数量少或表达不活跃的癌症患者，5年生存率比这种蛋白质数量多或表达活跃的患者要高。
研究发现，癌细胞中“PICT1”含量高的食道癌患者5年生存率为25%，而“PICT1”含量低的患者5年生存率可达到42%；直肠癌患者癌细胞内“PICT1”含量高和含量低的，5年生存率分别为62%和81%。
研究人员说，本项成果有助于抗癌新药的研发，以及进行更准确的癌症复发预测。(生物谷 Bioon.com)
doi:10.1038/nm.2392
PMC:
PMID:
Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11
Masato Sasaki; Kohichi Kawahara; Miki Nishio; Koshi Mimori; Ryunosuke Kogo; Koichi Hamada; Bunsho Itoh; Jia Wang; Yukako Komatsu; Yong Ryoul Yang; Hiroki Hikasa; Yasuo Horie; Takayuki Yamashita; Takehiko Kamijo; Yanping Zhang; Yan Zhu; Carol Prives; Toru Nakano; Tak Wah Mak; Takehiko Sasaki; Tomohiko Maehama; Masaki Mori; Akira Suzuki
PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus.
