Knockdown of PTK7 Reduces the Oncogenic Potential of Breast Cancer Cells by Impeding Receptor Tyrosine Kinase Signaling

• Published in: International journal of molecular sciences Vol. 24; no. 15; p. 12173
• Main Authors: Shin, Won-Sik, Oh, Si Won, Park, Han Na, Kim, Jae Hoon, Lee, Seung-Taek
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-07-2023; MDPI
• Subjects: Angiogenesis; Breast cancer; breast cancer (BC); Cell adhesion & migration; Cell growth; Cellular signal transduction; Comparative analysis; Epidermal growth factor; Esophageal cancer; Fibroblast growth factors; Growth factors; Kinases; Metastasis; Monoclonal antibodies; Mortality; Phenols; Phosphorylation; Polypeptides; protein tyrosine kinase 7 (PTK7); receptor tyrosine kinase (RTK); RNA; targeted therapy; triple-negative breast cancer (TNBC); Tumorigenesis; Tumors; Tyrosine; Womens health; Canada; South Korea; United States > US; targeted therapy; protein tyrosine kinase 7 (PTK7); breast cancer (BC); receptor tyrosine kinase (RTK); triple-negative breast cancer (TNBC)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241512173

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor tyrosine kinase (RTK), is often upregulated in various cancers. This study aimed to validate PTK7 as a target for breast cancer (BC) and investigate its oncogenic signaling mechanism. BC tissue analysis showed significantly elevated PTK7 mRNA levels, especially in refractory triple-negative breast cancer (TNBC) tissues, compared with normal controls. Similarly, BC cell lines exhibited increased PTK7 expression. Knockdown of PTK7 inhibited the proliferation of T-47D and MCF-7 hormone-receptor-positive BC cell-lines and of HCC1187, MDA-MB-231, MDA-MB-436, and MDA-MB-453 TNBC cells. PTK7 knockdown also inhibited the adhesion, migration, and invasion of MDA-MB-231, MDA-MB-436, and MDA-MB-453 cells, and reduced the phosphorylation levels of crucial oncogenic regulators including extracellular signal-regulated kinase (ERK), Akt, and focal adhesion kinase (FAK). Furthermore, PTK7 interacts with fibroblast growth factor receptor 1 (FGFR1) and epidermal growth factor receptor (EGFR) expressed in MDA-MB-231 cells. Knockdown of PTK7 decreased the growth-factor-induced phosphorylation of FGFR1 and EGFR in MDA-MB-231 cells, indicating its association with RTK activation. In conclusion, PTK7 plays a significant role in oncogenic signal transduction by enhancing FGFR1 and EGFR activation, influencing BC tumorigenesis and metastasis. Hence, PTK7 represents a potential candidate for targeted BC therapy, including TNBC.