PDF(Pubmed)
Abstract：
The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells\' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance. The transcriptional and posttranscriptional regulations of RKIP and PTEN expressions and their roles in resistance were reviewed. The underlying mechanism of the interrelationship between the signaling expressions of RKIP and PTEN in cancer is not clear. Several pathways are regulated by RKIP and PTEN and the transcriptional and post-transcriptional regulations of RKIP and PTEN is significantly altered in cancers. In addition, RKIP and PTEN play a key role in the regulation of tumor cells response to chemotherapy and immunotherapy. In addition, molecular and bioinformatic data revealed crosstalk signaling networks that regulate the expressions of both RKIP and PTEN. These crosstalks involved the mitogen-activated protein kinase (MAPK)/PI3K pathways and the dysregulated nuclear factor-kappaB (NF-κB)/Snail/Yin Yang 1 (YY1)/RKIP/PTEN loop in many cancers. Furthermore, further bioinformatic analyses were performed to investigate the correlations (positive or negative) and the prognostic significance of the expressions of RKIP or PTEN in 31 different human cancers. These analyses were not uniform and only revealed that there was a positive correlation between the expression of RKIP and PTEN only in few cancers. These findings demonstrated the existence of signaling cross-talks between RKIP and PTEN and both regulate resistance. Targeting either RKIP or PTEN (alone or in combination with other therapies) may be sufficient to therapeutically inhibit tumor growth and reverse the tumor resistance to cytotoxic therapies.
摘要：
据报道，Raf激酶抑制剂蛋白（RKIP）在许多癌症中表达不足，并在调节肿瘤细胞的存活中起作用。扩散,入侵,和转移，因此，肿瘤抑制剂.RKIP还调节肿瘤细胞对细胞毒性药物/细胞的抗性。同样，肿瘤抑制剂，磷酸酶和张力蛋白同源物（PTEN），抑制磷脂酰肌醇3激酶（PI3K）/AKT途径，要么是变异的，压力不足,或在许多癌症中删除，并与RKIP共享其抗肿瘤特性及其在抗性中的调节。综述了RKIP和PTEN表达的转录和转录后调控及其在抗性中的作用。RKIP和PTEN在癌症中的信号表达之间的相互关系的潜在机制尚不清楚。几种途径受RKIP和PTEN调节,并且RKIP和PTEN的转录和转录后调节在癌症中显著改变。此外,RKIP和PTEN在调节肿瘤细胞对化疗和免疫治疗的反应中起关键作用。此外,分子和生物信息学数据揭示了调节RKIP和PTEN表达的串扰信号网络。这些交联在许多癌症中涉及丝裂原活化蛋白激酶（MAPK）/PI3K途径和失调的核因子κB（NF-κB）/蜗牛/阴阳1（YY1）/RKIP/PTEN环。此外，我们进行了进一步的生物信息学分析,以研究RKIP或PTEN在31种不同人类癌症中表达的相关性(阳性或阴性)和预后意义.这些分析是不一致的,并且仅显示仅在少数癌症中RKIP和PTEN的表达之间存在正相关。这些发现证明了RKIP和PTEN之间存在信号交叉对话，并且两者都调节抗性。靶向RKIP或PTEN(单独或与其他疗法组合)可足以治疗性抑制肿瘤生长并逆转肿瘤对细胞毒性疗法的抗性。
