Functional roles of FAP-α in metabolism, migration and invasion of human cancer cells.
Functional roles of FAP-α in metabolism, migration and invasion of human cancer cells.
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FAP-α在代谢，人类癌细胞迁移和侵袭中的功能作用。
DOI：
10.3389/fonc.2023.1068405
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
成纤维细胞活化蛋白-α（FAP-α）是一种跨膜丝氨酸蛋白酶，由于其由在免疫抑制和癌症转移中起作用的癌症相关成纤维细胞亚群表达而引起了人们的极大兴趣。FAP-α也在一些癌细胞中表达，如黑素瘤、结直肠癌和乳腺癌细胞。三阴性乳腺癌（TNBC）是一种侵袭性癌症，迫切需要鉴定新的治疗靶点。为了扩大我们对FAP-α在TNBC中的功能作用的理解，我们设计了一种人TNBC细胞系MDA-MB-231，以稳定过表达FAP-α，并通过1H磁共振光谱、细胞增殖、以伤口愈合为特征的迁移和侵袭来表征代谢变化。FAP-α过度表达导致肌醇、胆碱代谢物、肌酸和牛磺酸的显著改变，以及迁移和侵袭的显著增加，尽管增殖保持不变。迁移和侵袭的增加与FAP-α作为外肽酶和内肽酶/明胶酶/胶原酶在组织重塑和修复以及细胞迁移中的已知活性一致。我们还确定了FAP-α过表达对人纤维肉瘤HT 1080细胞系的影响，该细胞系显示迁移增加，伴随着代谢的有限变化，确定了代谢变化对细胞类型的依赖性。这些代谢数据确定了FAP-α在本文研究的TNBC细胞系中修饰癌细胞代谢的先前未知作用，这可能为其在癌症进展中的功能作用提供新的见解。
Fibroblast activation protein-α (FAP-α) is a transmembrane serine protease that is attracting significant interest as it is expressed by a subgroup of cancer-associated fibroblasts that play a role in immune suppression and cancer metastasis. FAP-α is also expressed by some cancer cells, such as melanoma, colorectal and breast cancer cells. Triple negative breast cancer (TNBC) is an aggressive cancer that urgently requires identification of novel targets for therapy. To expand our understanding of the functional roles of FAP-α in TNBC we engineered a human TNBC cell line, MDA-MB-231, to stably overexpress FAP-α and characterized changes in metabolism by 1H magnetic resonance spectroscopy, cell proliferation, migration characterized by wound healing, and invasion. FAP-α overexpression resulted in significant alterations in myoinositol, choline metabolites, creatine, and taurine, as well as a significant increase of migration and invasion, although proliferation remained unaltered. The increase of migration and invasion are consistent with the known activities of FAP-α as an exopeptidase and endopeptidase/gelatinase/collagenase in tissue remodeling and repair, and in cell migration. We additionally determined the effects of FAP-α overexpression on the human fibrosarcoma HT1080 cell line that showed increased migration, accompanied by limited changes in metabolism that identified the dependency of the metabolic changes on cell type. These metabolic data identify a previously unknown role of FAP-α in modifying cancer cell metabolism in the TNBC cell line studied here that may provide new insights into its functional roles in cancer progression.
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影响因子：
5
作者：
Almansour NM
通讯作者：
Almansour NM
DOI：
10.1016/s0006-291x(02)00920-8
发表时间：
2002-08-23
影响因子：
3.1
作者：
Ramírez de Molina, A;Rodríguez-González, A;Lacal, JC
通讯作者：
Lacal, JC
成纤维细胞激活蛋白调节肿瘤相关成纤维细胞和上皮性卵巢癌细胞
影响因子：
5.2
作者：
Lai, Dongmei;Ma, Li;Wang, Fangyuan
通讯作者：
Wang, Fangyuan
影响因子：
8
作者：
Ramirez-Montagut, T;Blachere, NE;Houghton, AN
通讯作者：
Houghton, AN
FAP-α（成纤维细胞激活蛋白-α）通过FAK途径控制人类乳腺癌细胞系的生长和运动性。
影响因子：
--
作者：
Jia J;Martin TA;Ye L;Jiang WG
通讯作者：
Jiang WG