被诊断患有晚期转移性结直肠癌（CRC）的患者面临着以低生存率为特征的暗淡预后。失巢凋亡（转移性癌细胞表现出的程序性凋亡抵抗）是这种情况下的一个关键因素。我们采用了批量流式细胞术和 RT-qPCR 检测，对小鼠和斑马鱼进行了体内实验，并分析了患者组织以检查失巢凋亡的影响。 B 细胞特异性莫洛尼鼠白血病病毒插入位点 1 (Bmi1)-中期因子 (MDK) 轴对失巢凋亡的细胞反应。 Bmi1 在肿瘤发生中至关重要。本研究阐明了 Bmi1 在赋予 CRC 失巢凋亡抵抗中的作用，并探讨了其与转移相关的下游靶标。Bmi1 表达水平升高与 CRC 的远处转移相关。 Bmi1 的抑制显着降低了 CRC 细胞的转移潜力。 Bmi1 的抑制导致从基质脱离的凋亡 SW620 细胞的比例增加。添加拓扑异构酶 I 抑制剂伊立替康进一步增强了这种效果。此外，Bmi1 被发现与 MDK 协同调节 CRC 活力，在体内模型和临床组织标本中观察到一致的表达模式。总之，Bmi1 通过赋予失巢凋亡抵抗力来调节 CRC 转移能力。此外，它与 MDK 合作促进侵袭和远处转移。在对晚期 CRC 患者进行传统化疗方案时，靶向 Bmi1 可能提供一种有前景的辅助治疗策略。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士） ， 版权所有。

Patients diagnosed with advanced metastatic colorectal cancer (CRC) confront a bleak prognosis characterized by low survival rates. Anoikis, the programmed apoptosis resistance exhibited by metastatic cancer cells, is a crucial factor in this scenario.We employed bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to examine the effects of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis on the cellular response to anoikis. Bmi1 is pivotal in tumorigenesis. This study elucidated the involvement of Bmi1 in conferring anoikis resistance in CRC and explored its downstream targets associated with metastasis.Elevated levels of Bmi1 expression correlated with distant metastasis in CRC. Suppression of Bmi1 significantly diminished the metastatic potential of CRC cells. Inhibition of Bmi1 led to an increase in the proportion of apoptotic SW620 cells detached from the matrix. This effect was further enhanced by the addition of irinotecan, a topoisomerase I inhibitor. Furthermore, Bmi1 was found to synergize with MDK in modulating CRC viability, with consistent expression patterns observed in in vivo models and clinical tissue specimens. In summary, Bmi1 acted as a regulator of CRC metastatic capability by conferring anoikis resistance. Additionally, it collaborated with MDK to facilitate invasion and distant metastasis.Targeting Bmi1 may offer a promising adjunctive therapeutic strategy when administering traditional chemotherapy regimens to patients with advanced CRC.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.