Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 90-363 Lodz, Poland.
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.
Int J Mol Sci. 2024 Nov 19;25(22):12433. doi: 10.3390/ijms252212433.
The migratory and invasive capabilities of melanoma cells contribute to metastasis. Therefore, targeting the genes driving these processes can support melanoma therapy. Rab27A and Rab27B contribute to tumor formation progression in many types of cancer through various mechanisms, including the secretion of small extracellular vesicles (sEVs). We explored the role of these GTPases in melanoma cell functioning in three RAB27A knockout (KO) cell lines (A375, DMBC12, and SkMel28) and a double RAB27A/B KO A375 cell line. The loss of RAB27A impaired the migration and invasion of DMBC12 and SkMel28 cells; however, the behavior of highly aggressive A375 cells was unaffected. The RAB27A/B double knockout moderately decreased the migratory capacity of A375 cells without disturbing their invasiveness. Additionally, the silencing of RAB27A did not affect the number and mean size of the sEVs, despite some alterations in the protein content of the vesicles. Both Rab27 isoforms can, at least partially, act independently. The potential role of Rab27A in the functioning of melanoma cells depends on the individual character of the cell line, but not on its basal expression, and seems to be unrelated to the secretion of sEVs.
黑素瘤细胞的迁移和侵袭能力有助于转移。因此，针对驱动这些过程的基因可以支持黑色素瘤的治疗。Rab27A 和 Rab27B 通过多种机制，包括分泌小细胞外囊泡 (sEVs)，促进多种类型癌症的肿瘤形成和进展。我们在三个 RAB27A 敲除 (KO) 细胞系 (A375、DMBC12 和 SkMel28) 和一个 RAB27A/B 双敲除 A375 细胞系中探索了这些 GTPase 在黑素瘤细胞功能中的作用。Rab27A 的缺失削弱了 DMBC12 和 SkMel28 细胞的迁移和侵袭能力；然而，高侵袭性的 A375 细胞的行为不受影响。RAB27A/B 双敲除适度降低了 A375 细胞的迁移能力，而不影响其侵袭性。此外，Rab27A 的沉默并不影响 sEVs 的数量和平均大小，尽管囊泡的蛋白含量有一些改变。两种 Rab27 同工型至少可以部分独立发挥作用。Rab27A 在黑素瘤细胞功能中的潜在作用取决于细胞系的个体特征，而与细胞的基础表达无关，并且似乎与 sEVs 的分泌无关。
