Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, Shahekou District, Dalian City, 116027, Liaoning Province, China.
Mol Med. 2020 Apr 5;26(1):27. doi: 10.1186/s10020-020-00158-2.
Tissue factor pathway inhibitor 2 (TFPI2) participates in carcinogenesis of various tumors, and is associated with poor survival of breast cancer patients. However, the effect and underlying mechanism of TFPI2 on breast cancer progression remains to be investigated.
The expression level of TFPI2 in breast cancer tissues and cell lines was examined via qRT-PCR (quantitative real-time polymerase chain reaction) and immunohistochemistry. CCK8 (Cell Counting Kit-8), colony formation, wound healing or transwell assays were used to detect cell viability, proliferation, migration or invasion, respectively. In vivo subcutaneous xenotransplanted tumor model was established to detect tumorigenic function of TFPI2, and the underlying mechanism was evaluated by immunohistochemistry and western blot.
TFPI2 was down-regulated in breast cancer tissues and cell lines, and was associated with poor prognosis of patients diagnosed with breast cancer. Over-expression of TFPI2 inhibited cell viability, proliferation, migration and invasion of breast cancer cells. Mechanistically, Twist-related protein 1 (TWIST1) was negatively associated with TFPI2 in breast cancer patients, whose expression was decreased by TFPI2 over-expression or increased by TFPI2 knockdown. Moreover, TWIST1 could up-regulate integrin α5 expression. Functional assays indicated that the inhibition abilities of TFPI2 over-expression on breast cancer progression were reversed by TWIST1 over-expression. In vivo subcutaneous xenotransplanted tumor model also revealed that over-expression of TFPI2 could suppress breast tumor growth via down-regulation of TWIST1-mediated integrin α5 expression.
TFPI2 suppressed breast cancer progression through inhibiting TWIST-integrin α5 pathway, providing a new potential therapeutic target for breast cancer treatment.
组织因子途径抑制物 2（TFPI2）参与多种肿瘤的发生，与乳腺癌患者的不良预后相关。然而，TFPI2 对乳腺癌进展的影响及其潜在机制仍有待研究。
通过 qRT-PCR（实时定量聚合酶链反应）和免疫组织化学检测乳腺癌组织和细胞系中 TFPI2 的表达水平。CCK8（细胞计数试剂盒-8）、集落形成、划痕愈合或 Transwell 分析分别用于检测细胞活力、增殖、迁移或侵袭。建立体内皮下异种移植肿瘤模型，以检测 TFPI2 的致瘤功能，并通过免疫组织化学和 Western blot 评估其潜在机制。
TFPI2 在乳腺癌组织和细胞系中下调，与乳腺癌患者的不良预后相关。TFPI2 的过表达抑制乳腺癌细胞的活力、增殖、迁移和侵袭。机制上，TWIST 相关蛋白 1（TWIST1）在乳腺癌患者中与 TFPI2 呈负相关，其表达被 TFPI2 过表达下调或被 TFPI2 敲低上调。此外，TWIST1 可以上调整合素 α5 的表达。功能分析表明，TWIST1 过表达逆转了 TFPI2 过表达对乳腺癌进展的抑制作用。体内皮下异种移植肿瘤模型也表明，TFPI2 的过表达通过下调 TWIST1 介导的整合素 α5 表达抑制乳腺癌肿瘤生长。
TFPI2 通过抑制 TWIST-整合素 α5 通路抑制乳腺癌进展，为乳腺癌治疗提供了一个新的潜在治疗靶点。
