Fu Fangmei, Yang Xudong, Zheng Minying, Zhao Qi, Zhang Kexin, Li Zugui, Zhang Hao, Zhang Shiwu
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Tianjin Rehabilitation Center, Tianjin, China.
Front Mol Biosci. 2020 Aug 18;7:202. doi: 10.3389/fmolb.2020.00202. eCollection 2020.
Transmembrane 4 L six family 1 (TM4SF1) is a protein with four transmembrane domains that belongs to the transmembrane 4 L six family members (TM4SFs). Structurally, TM4SF1 consists of four transmembrane domains (TM1-4), N- and C-terminal intracellular domains, two extracellular domains, a smaller domain between TM1 and TM2, and a larger domain between TM3 and TM4. Within the cell, TM4SF1 is located at the cell surface where it transmits extracellular signals into the cytoplasm. TM4SF1 interacts with tetraspanins, integrin, receptor tyrosine kinases, and other proteins to form tetraspanin-enriched microdomains. This interaction affects the pro-migratory activity of the cells, and thus it plays important roles in the development and progression of cancer. TM4SF1 has been shown to be overexpressed in many malignant tumors, including gliomas; malignant melanomas; and liver, prostate, breast, pancreatic, bladder, colon, lung, gastric, ovarian, and thyroid cancers. TM4SF1 promotes the migration and invasion of cancer cells by inducing epithelial-mesenchymal transition, self-renewal ability, tumor angiogenesis, invadopodia formation, and regulating the related signaling pathway. TM4SF1 is an independent prognostic indicator and biomarker in several cancers. It also promotes drug resistance, which is a major cause of therapeutic failure. These characteristics make TM4SF1 an attractive target for antibody-based immunotherapy. Here, we review the many functions of TM4SF1 in malignant tumors, with the aim to understand the interaction between its expression and the biological behaviors of cancer and to supply a basis for exploring new therapeutic targets.
跨膜4 L六家族成员1（TM4SF1）是一种具有四个跨膜结构域的蛋白质，属于跨膜4 L六家族成员（TM4SFs）。从结构上看，TM4SF1由四个跨膜结构域（TM1 - 4）、N端和C端细胞内结构域、两个细胞外结构域、TM1和TM2之间的一个较小结构域以及TM3和TM4之间的一个较大结构域组成。在细胞内，TM4SF1位于细胞表面，在那里它将细胞外信号传递到细胞质中。TM4SF1与四跨膜蛋白、整合素、受体酪氨酸激酶和其他蛋白质相互作用，形成富含四跨膜蛋白的微结构域。这种相互作用影响细胞的促迁移活性，因此在癌症的发生和发展中起重要作用。TM4SF1已被证明在许多恶性肿瘤中过度表达，包括神经胶质瘤、恶性黑色素瘤以及肝癌、前列腺癌、乳腺癌、胰腺癌、膀胱癌、结肠癌、肺癌、胃癌、卵巢癌和甲状腺癌。TM4SF1通过诱导上皮 - 间质转化、自我更新能力、肿瘤血管生成、侵袭伪足形成以及调节相关信号通路来促进癌细胞的迁移和侵袭。TM4SF1是几种癌症中的独立预后指标和生物标志物。它还促进耐药性，这是治疗失败的主要原因。这些特性使TM4SF1成为基于抗体的免疫治疗的有吸引力的靶点。在此，我们综述TM4SF1在恶性肿瘤中的多种功能，旨在了解其表达与癌症生物学行为之间的相互作用，并为探索新的治疗靶点提供依据。
