Background/Objectives: Fibrillarin (FBL) is a key nucleolar methyltransferase involved in ribosome biogenesis through 2′-O-ribose methylation of rRNA. While its oncogenic role has been reported in several cancer types, its expression and function in human colorectal cancer (CRC) have remained largely unexplored. This study aims to investigate the expression of FBL in human CRC tissues and cell lines and to determine its functional role in tumor progression and metastasis. Methods: We examined FBL expression in paired human CRC primary tumors and liver metastases using immunohistochemistry. Functional studies were performed using SW-480 (primary tumor) and SW-620 (lymph node metastasis) CRC cell lines derived from the same patient. Cell migration, invasion, and 3D spheroid growth were analyzed following FBL downregulation. In vivo tumor growth was assessed in SCID mice xenografted with FBL-deficient cells. Molecular changes were explored through phosphorylation arrays and Western blotting. Results: FBL expression was significantly higher in human metastatic lesions than in primary tumors. FBL downregulation impaired migration, invasion, and spheroid growth in SW-480 and SW-620 cells and reduced tumor growth in vivo. Mechanistically, FBL inhibition decreased activation of MAPK/ERK, PI3K/AKT, and JNK/p38 pathways and reduced phosphorylation of the transcription factor CREB. Conclusions: Our study identifies FBL as a potential contributor to colorectal cancer progression, with elevated expression associated particularly with metastatic disease. By demonstrating that FBL expression is elevated in patient-derived metastatic tissues and functionally promotes migration, invasion, and tumor growth, our findings expand the role of ribosome biogenesis factors beyond protein synthesis. The observed suppression of key oncogenic pathways and CREB phosphorylation upon FBL inhibition suggests that FBL integrates ribosomal regulation with cancer cell signaling. These insights open new avenues for targeting nucleolar activity in advanced CRC and highlight FBL as a potential biomarker and therapeutic target in metastatic disease.
**背景/目的：** 纤维蛋白（FBL）是一种关键的核仁甲基转移酶，通过rRNA的2′-O-核糖甲基化参与核糖体生物合成。尽管其致癌作用已在多种癌症类型中被报道，但其在人类结直肠癌（CRC）中的表达和功能在很大程度上仍未得到探索。本研究旨在探讨FBL在人类CRC组织和细胞系中的表达，并确定其在肿瘤进展和转移中的功能作用。 **方法：** 我们使用免疫组织化学方法检测了配对的人类CRC原发肿瘤和肝转移灶中FBL的表达。功能研究使用源自同一患者的SW-480（原发肿瘤）和SW-620（淋巴结转移）CRC细胞系进行。在FBL下调后，分析了细胞迁移、侵袭和3D球体生长。在移植了FBL缺陷细胞的SCID小鼠中评估了体内肿瘤生长。通过磷酸化蛋白芯片和蛋白质印迹法探索了分子变化。 **结果：** FBL在人类转移灶中的表达显著高于原发肿瘤。FBL下调损害了SW-480和SW-620细胞的迁移、侵袭和球体生长能力，并减少了体内肿瘤生长。机制上，抑制FBL降低了MAPK/ERK、PI3K/AKT和JNK/p38通路的激活，并减少了转录因子CREB的磷酸化。 **结论：** 我们的研究确定FBL是结直肠癌进展的潜在促进因子，其表达升高尤其与转移性疾病相关。通过证明FBL在患者来源的转移组织中表达升高，并在功能上促进迁移、侵袭和肿瘤生长，我们的发现拓展了核糖体生物合成因子在蛋白质合成之外的作用。在FBL抑制后观察到关键致癌通路和CREB磷酸化的抑制，表明FBL将核糖体调控与癌细胞信号传导整合在一起。这些见解为靶向晚期CRC的核仁活性开辟了新途径，并突显了FBL作为转移性疾病中潜在生物标志物和治疗靶点的价值。
肿瘤(癌症)患者之家