失去附着能够促进癌细胞内前列氨酸的积累和排泄。
Loss of attachment promotes proline accumulation and excretion in cancer cells.
发表日期:2023 Sep 08
作者:
Steven E Pilley, Marc Hennequart, Anke Vandekeere, Julianna Blagih, Nathalie M Legrave, Sarah-Maria Fendt, Karen H Vousden, Christiaan F Labuschagne
来源:
Protein & Cell
摘要:
以前的研究已经揭示了脯氨酸代谢在支持癌症发展和转移中的作用。在本研究中,我们展示了许多癌细胞在失去附着后会积累和分泌脯氨酸。与附着细胞相比,脱附细胞显示出减少的增殖能力,伴随着总体蛋白质产量和新生氨基酸合成的普遍减少。然而,在脱附条件下,脯氨酸合成仍然保持稳定。此外,尽管脱附细胞中总体脯氨酸并入蛋白质的量较其他氨基酸较低,但脯氨酸丰富的蛋白质胶原的产生增加了。脱附细胞增加的脯氨酸排泄还被证明被肿瘤微环境中丰富且重要的巨噬细胞利用。我们的研究表明,脱附诱导的脯氨酸积累和分泌可能通过支持细胞外基质的增加生产和为周围基质细胞提供脯氨酸来促进肿瘤发展。
Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline incorporation into proteins was lower in detached cells compared to other amino acids, there was an increased production of the proline-rich protein collagen. The increased excretion of proline from detached cells was also shown to be used by macrophages, an abundant and important component of the tumor microenvironment. Our study suggests that detachment induced accumulation and secretion of proline may contribute to tumor progression by supporting increased production of extracellular matrix and providing proline to surrounding stromal cells.