Therapeutic Potential of Protein Tyrosine Kinase 6 in Colorectal Cancer

SIMPLE SUMMARY: Protein tyrosine kinase 6 (PTK6) is a biomarker of poor prognosis in breast cancer, but its importance in other cancer types is unclear. In this review, we explore a potential role for PTK6 in colorectal cancer. PTK6 phosphorylates multiple substrates, including signal transduction proteins, RNA binding proteins, and transcription factors, many of which are involved in key colorectal cancer pathways. PTK6 is overexpressed in colorectal tumors vs. normal tissue and activates WNT signaling when localized to the membrane in colorectal cancer cells. It is also upregulated and promotes cell survival under DNA-damaging conditions. We propose that targeting PTK6 therapeutically in colorectal cancer could increase cancer cell sensitivity to standard chemotherapy treatment. ABSTRACT: PTK6, a non-receptor tyrosine kinase, modulates the pathogenesis of breast and prostate cancers and is recognized as a biomarker of breast cancer prognosis. There are over 30 known substrates of PTK6, including signal transducers, transcription factors, and RNA-binding proteins. Many of these substrates are known drivers of other cancer types, such as colorectal cancer. Colon and rectal tumors also express higher levels of PTK6 than the normal intestine suggesting a potential role in tumorigenesis. However, the importance of PTK6 in colorectal cancer remains unclear. PTK6 inhibitors such as XMU-MP-2 and Tilfrinib have demonstrated potency and selectivity in breast cancer cells when used in combination with chemotherapy, indicating the potential for PTK6 targeted therapy in cancer. However, most of these inhibitors are yet to be tested in other cancer types. Here, we discuss the current understanding of the function of PTK6 in normal intestinal cells compared with colorectal cancer cells. We review existing PTK6 targeting therapeutics and explore the possibility of PTK6 inhibitory therapy for colorectal cancer.