虽然已知癌症转移是癌症相关死亡的主要原因，但是癌症转移的具体机制尚不明确。既往研究发现，核糖体是催化蛋白质合成的细胞器，由小的40S亚基和大的60S亚基组成，60S酸性核糖体蛋白RPLP1是核糖体蛋白质家族成员之一，与肿瘤发生和初生细胞的无限增殖化相关，并参与良性细胞向恶性细胞的转化。不过，三阴性乳腺癌的RPLP1表达水平和潜在功能仍不清楚。
2018年10月25日，施普林格与英国《自然》旗下生物医学中心《国际癌细胞》在线发表复旦大学附属肿瘤医院、南通大学附属医院、南通大学第四附属医院暨盐城市第一人民医院的研究报告，发现RPLP1可以促进肿瘤转移并与三阴性乳腺癌患者不良预后相关。
该研究通过实时聚合酶链反应和蛋白质免疫印迹法，三阴性乳腺癌组织和细胞株的RPLP1表达进行检测。通过免疫化学对81例三阴性乳腺癌组织标本及其相邻非肿瘤组织标本进行检测，以确定RPLP1表达与临床病理学特征之间的相关性。通过体外实验，确定RPLP1对三阴性乳腺癌细胞株肿瘤转移的作用和机制途径。
结果，三阴性乳腺癌标本和细胞株检出高水平的RPLP1表达。三阴性乳腺癌组织和细胞的RPLP1水平提高，并且表达水平高与复发和转移的风险增加相关。此外，RPLP1高表达与不良预后相关，并且是三阴性乳腺癌的独立预后标志。在RPLP1诱发的癌症转移中，RPLP1可以增强癌细胞侵袭，这可能是其影响癌细胞上皮→间质转化的结果。
因此，该研究结果表明，RPLP1有望成为三阴性乳腺癌不良预后的潜在生物标志和防止转移的候选治疗靶点。
Cancer Cell Int. 2018 Oct 25;18:170.
RPLP1 promotes tumor metastasis and is associated with a poor prognosis in triple-negative breast cancer patients.
He Z, Xu Q, Wang X, Wang J, Mu X, Cai Y, Qian Y, Shao W, Shao Z.
Shanghai Cancer Center, Fudan University, Shanghai, China; Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; The Fourth Affiliated Hospital of Nantong University, Yancheng, Jiangsu, China.
BACKGROUND: Cancer metastasis is the major reason for cancer related deaths, and the mechanism of cancer metastasis still unclear. RPLP1, a member of a group of proteins known as ribosomal proteins, is associated with tumorigenesis and primary cell immortalization and is involved in cellular transformation. However, the expression and potential function of RPLP1 in TNBC remain unclear.
METHODS: The expression of RPLP1 in TNBC tissues and cell lines were detected with Real-Time PCR and western blotting. 81 cases of TNBC tissue samples and adjacent non-tumor tissue samples were tested by immunochemistry to determine the correlation between the RPLP1 expression and clinicopathological characteristics. In vitro, we determined the role and mechanistic pathways of RPLP1 in tumor metastasis in TNBC cell lines.
RESULTS: In this study, we detected high levels of RPLP1 expression in TNBC samples and cell lines. RPLP1 is upregulated in triple-negative breast cancer (TNBC) tissues and cells, and high expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, high RPLP1 expression was associated with a poor prognosis and was an independent prognostic marker for TNBC. In RPLP1-induced cancer metastasis, RPLP1 may increase cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition.
CONCLUSIONS: Altogether, our findings indicate RPLP1 is a poor prognostic potential biomarker and anti-metastasis candidate therapeutic target in triple-negative breast cancer.
KEYWORDS: Epithelial-mesenchymal transition; RPLP1; Triple-negative breast cancer
PMID: 30386179
PMCID: PMC6203216
DOI: 10.1186/s12935-018-0658-0
联系客服
