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首页> 外文期刊>Cancer Management and Research >SSBP1 Upregulation In Colorectal Cancer Regulates Mitochondrial Mass
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SSBP1 Upregulation In Colorectal Cancer Regulates Mitochondrial Mass

机译：结肠直肠癌的SSBP1上调调节线粒体质量

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Background: Colorectal cancers (CRC) are one of the most common forms of cancer seen worldwide, and also remain difficult to treat despite recent advances in chemotherapy. Although significant progress has been made in recent years towards precision medicine and mutation-guided therapy, common mechanisms that underlie tumor growth and progression remain incompletely understood. Methods: Tumor tissue and nearby unaffected tissue were collected from 15 patients at each stage of CRC, from which we generated representative proteomics profiles of three stages. Bioinformatics analysis was performed to discover common differences that may be shared between the representative profiles and across larger cohorts. Flow cytometry was then used to identify functional consequences of SSBP1 depletion in cell lines, since its expression level was consistently increased in tumor cells across all of the datasets analyzed. Results: Direct comparison of CRC tumor and unaffected tissue at each stage demonstrated that a number of proteins involved in mitochondrial function displayed significantly altered expression patterns. Depletion of SSBP1 in colon cancer cell lines was able to trigger loss of mitochondrial mass and an increase in tumor cell death, and this effect that was further accentuated in the presence of the common chemotherapy drug cisplatin. Conclusion: Mitochondrial biogenesis and maintenance may play an important part in tumor cell survival during CRC progression, and may be a useful target for directed inhibition or adjuvant targeting in the cases of cisplatin resistance.
机译：背景：结直肠癌（CRC）是全球最常见的癌症中最常见的癌症之一，尽管最近的化疗进展，但仍然难以治疗。近年来近年来对精密药物和突变引导的治疗进行了重大进展，但肿瘤生长和进展的常见机制仍然不完全理解。方法：从CRC的每个阶段的> 15名患者中收集肿瘤组织和附近未受影响的组织，从中产生三个阶段的代表性蛋白质组学谱。进行生物信息学分析，以发现可以在代表性概况和较大的队列之间共享的常见差异。然后使用流式细胞术用于鉴定细胞系中SSBP1耗竭的功能后果，因为其在分析的所有数据集中在肿瘤细胞中始终如一地增加。结果：每阶段的CRC肿瘤和未受影响的组织的直接比较表明，许多参与线粒体函数的蛋白质显着改变了表达模式。结肠癌细胞系的SSBP1耗尽能够引发线粒体肿块的丧失和肿瘤细胞死亡的增加，并且在常见化疗药物顺铂存在下进一步突出的这种效果。结论：线粒体生物发生和维持可在CRC进展期间在肿瘤细胞存活中发挥重要组成部分，并且可以是在顺铂抗性病例中定向抑制或佐剂靶向的有用靶标。

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