Cui Nai-Peng, Qiao Shu, Jiang Shan, Hu Jin-Lin, Wang Ting-Ting, Liu Wen-Wen, Qin Yan, Wang Ya-Nan, Zheng Li-Shuang, Zhang Jin-Chao, Ma Yong-Ping, Chen Bao-Ping, Shi Jian-Hong
Department of Breast Surgery, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, China.
Institute of Life Science and Green Development, Hebei University, Baoding, China.
Front Oncol. 2021 Jul 22;11:699889. doi: 10.3389/fonc.2021.699889. eCollection 2021.
Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC.
Correlation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity .
PTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression .
This study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression EGFR/Akt signaling pathway.
三阴性乳腺癌（TNBC）是乳腺癌中侵袭性最强的亚型，具有高侵袭性、高转移发生率和不良预后。蛋白酪氨酸激酶7（PTK7）在多种癌症中起重要作用。然而，PTK7在TNBC中的作用尚未得到充分研究。本研究旨在评估PTK7在TNBC进展中的作用。
采用组织芯片免疫组化（IHC）染色评估280例乳腺癌患者中PTK7表达与临床病理参数的相关性。使用免疫印迹法检测TNBC（MDA-MB-468、MDA-MB-436和MDA-MB-231）和非TNBC（MCF7和SK-BR-3）乳腺癌细胞系中PTK7的表达。利用包括1904例患者的cBioPortal乳腺癌数据集分析浸润性乳腺癌中与PTK7相关的基因。使用PTK7过表达或敲低的TNBC细胞系（MDA-MB-468和MDA-MB-436）分析PTK7在TNBC转移和肿瘤进展中的潜在作用。建立TNBC荷瘤小鼠模型以进一步分析PTK7在TNBC致瘤性中的作用。
PTK7在乳腺癌中高表达，与较差的预后相关，并与TNBC中的肿瘤转移和进展相关。TNBC细胞系中PTK7的共表达分析以及功能获得或丧失研究表明，PTK7参与EGFR/Akt信号调节，并与乳腺癌中的细胞外基质组织和迁移基因相关，包括COL1A1、FN1、WNT5B、MMP11、MMP14和SDC1。PTK7的功能获得或丧失实验表明，PTK7促进TNBC细胞系的增殖和迁移。PTK7敲低的MDA-MB-468细胞荷瘤小鼠模型进一步证明，PTK7缺陷抑制TNBC肿瘤进展。
本研究确定PTK7为TNBC预后较差的潜在标志物，并揭示PTK7通过EGFR/Akt信号通路促进TNBC转移和进展。
