Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Int Immunopharmacol. 2023 Mar;116:109743. doi: 10.1016/j.intimp.2023.109743. Epub 2023 Jan 25.
Cell metastasis is the main cause of cancer mortality. Inhibiting early events during cell metastasis and invasion could significantly improve cancer prognosis, but the initial mechanisms of cell transition and migration are barely known. Calcium regulates cell migration, whilst Thymosin β4 is a G-actin and iron binding peptide associated with tumor metastasis and ferroptosis. Under normal cell growth conditions, intracellular free calcium ions and Thymosin β4 concentrations are strictly regulated, and are not influenced by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 and increases extracellular peptide uptake above the normal range. Unexpectedly, cell starvation significantly increases internalization of extracellular Ca/Thymosin β4 complexes. Elucidating the role of Ca/Thymosin β4 in the early events of metastasis will likely be important in the future to develop therapies targeting metastasis.
细胞转移是癌症死亡的主要原因。抑制细胞转移和侵袭的早期事件可以显著改善癌症的预后，但细胞转化和迁移的初始机制几乎未知。钙调节细胞迁移，而胸腺肽 β4 是一种与肿瘤转移和铁死亡相关的 G-肌动蛋白和铁结合肽。在正常细胞生长条件下，细胞内游离钙离子和胸腺肽 β4 浓度受到严格调节，不受细胞外补充的影响。然而，细胞饥饿会降低细胞内的胸腺肽 β4 浓度，并增加细胞外肽的摄取量，使其超过正常范围。出乎意料的是，细胞饥饿会显著增加细胞对外源 Ca/胸腺肽 β4 复合物的内化。阐明 Ca/胸腺肽 β4 在转移早期事件中的作用，对于未来开发针对转移的治疗方法可能非常重要。
