PTK7

OVERVIEW

PTK7 is a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, which has been shown preclinically to be enriched on tumor initiating cells (TICs) in several tumor types.¹

Protein tyrosine kinase 7 (PTK7) belongs to the receptor tyrosine kinase family with an inactive kinase domain²
PTK7, also known as colon carcinoma kinase 4 (CCK-4), is upregulated in various cancers, where it is known to act as either an oncoprotein or a tumor suppressor³

IMPLICATIONS IN CANCER

An unbiased analysis of isolated TIC populations provided the first indication that PTK7 is enriched on TICs.¹
Next-generation whole transcriptome sequencing of functionally tumorigenic cell subpopulations showed higher PTK7 expression on TICs from triple negative breast cancer (TNBC) and ovarian cancer patient-derived xenografts compared to normal tissues.¹
PTK7 is also highly overexpressed in a variety of tumors, such as colon cancer, lung adenocarcinoma, acute myelogenous leukemia, and gastric cancer.²
Knocking down PTK7 expression in esophageal squamous cell carcinoma (ESCC) stem-like cells reduced their sphere formation, promoted apoptosis, and suppressed their migration and invasion abilities.⁴
- Knocking down PTK7 also inhibits tumor progression in TNBC.⁵

Oncogenic Expression

TNBC

In a panel of protein lysates from derived xenografts PTK7 expression was observed in 12 of 12 (100%) patient-derived xenografts.
PTK7 not only correlates with worse prognosis, but also associates with tumor metastasis and progression.⁵
PTK7 promotes cancer proliferation and migration.⁵

NSCLC

In a panel of protein lysates from derived xenografts higher PTK7 expression in NSCLC is associated with significantly shorter survival and it was observed that PTK7 enriches for TICs in NSCLC.¹
Studies have demonstrated that inhibition of PTK7 reduces the number of TICs and induces tumor regression.⁶

OVARIAN

In a panel of protein lysates from derived xenografts PTK7 expression was observed in 43 of 47 (91%) patient-derived xenografts.¹

Related Research

Tumor Antigen Targeting

Antibody-Drug Conjugates

Damelin M, et al. A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Sci Transl Med. 2017;9(372). pii: eaag2611.
Sun J-J, et al. The increased PTK7 expression is a malignant factor in cervical cancer. Hindawi Disease Markers. Volume 2019. Article ID 5380197. 10 pages.
Shin W-S, et al. Biphasic regulation of tumorigenesis by PTK7 expression level in esophageal squamous cell carcinoma. Scientific Reports. Volume 8. Article number: 8519 (2018).
Bie J, et al. PTK7 promotes the malignant properties of cancer stem-like cells in esophageal squamous cell lines. Human cell. 2020 Apr;33(2):356-65.
Cui NP, et al. Protein tyrosine kinase 7 (PTK7) regulates EGFR/Akt signaling pathway and correlates with malignant progression in triple-negative breast cancer. Frontiers in Oncology. 2021;11:2887.
Chen B, et al. Immune related genes and gene sets for predicting the response to anti programmed death 1 therapy in patients with primary or metastatic non small cell lung cancer. Oncology Letters. 2021 Jul 1;22(1):1-2.