Abstract
Thymosin β4 (Tβ4) is a small, 44-amino acid polypeptide. It has been implicated in multiple processes, including cell movement, angiogenesis, and stemness. Previously, we reported that melanoma cell lines differ in Tβ4 levels. Studies on stable clones with silenced TMSB4X expression showed that Tβ4 impacted adhesion and epithelial-mesenchymal transition progression. Here, we show that the cells with silenced TMSB4X expression exhibited altered actin cytoskeleton’s organization and subcellular relocalization of two intermediate filament proteins: Nestin and Vimentin. The rearrangement of the cell cytoskeleton resulted in changes in the cells’ topology, height, and stiffness defined by Young’s modulus. Simultaneously, only for some A375 clones with a lowered Tβ4 level, we observed a decreased ability to initiate colony formation in soft agar, tumor formation in vivo, and alterations in Nanog’s expression level transcription factor regulating stemness. Thus, we show for the first time that in A375 cells, biomechanical properties are not directly coupled to stemness features, and this cell line is phenotypically heterogeneous.
Highlights
Thymosin β4 (Tβ4) belongs to the β thymosin family of structurally related, hormonelike, highly conserved polypeptides [1]
To analyze the functions of Tβ4, we examined melanoma cell lines differing in the level of expression of this polypeptide
We continued the study on the role of Tβ4 in melanoma tumorigenesis using, as previously, the two melanoma cell lines: WM1341D, which is characterized by a low expression of TMSB4X, and A375, which was shown to have a higher expression level of TMSB4X [8]
Summary
Thymosin β4 (Tβ4) belongs to the β thymosin family of structurally related, hormonelike, highly conserved polypeptides [1]. Tβ4 was identified as the significant sequestering agent of monomeric actin (G-actin) in mammalian cells, directly involved in the actin cytoskeleton’s reorganization during cell movement [2] It plays an essential and complex role in wound healing: migration of keratinocytes and endothelial cells [3], stimulation of angiogenesis [4], recruiting and supporting the differentiation of progenitor cells at the injury site [5], reducing inflammation [6], and immunomodulatory activity [7]. These properties of Tβ4 raised questions about its role in cancer development and progression. We observed that the silencing of TMSB4X expression in melanoma cells affected their adhesion, migration, and invasion abilities
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