BRK

BRK (BReast tumor Kinase), also known as PTK6 (Protein Tyrosine Kinase 6), is a non-receptor tyrosine kinase that consists of three functional domains: SH3, SH2, and SH1 (tyrosine kinase). Unlike Src family tyrosine kinases, BRK lacks an N-terminal myristoylation site, making it more soluble and facilitating its interaction with intracellular substrates. In normal tissues, BRK expression is low, but it is highly upregulated in various tumors, including breast, ovarian, and cervical cancers, where its expression is associated with tumor malignancy and poor prognosis.
BRK exerts its oncogenic effects primarily by promoting proliferation, inhibiting apoptosis, enhancing invasion, and contributing to drug resistance. It activates multiple signaling pathways, including EGFR, HER2, IGF-1R, STAT3, and Akt, while suppressing tumor suppressors such as p27 and Rb, thereby facilitating cell cycle progression. Additionally, BRK regulates Paxillin, FAK, and RhoA, promoting cell migration and invasion, and is induced under hypoxic conditions by HIF-1α, further accelerating tumor metastasis. BRK also influences chemotherapy resistance, as its high expression reduces sensitivity to anti-HER2 and anti-EGFR compounds. Therefore, BRK is considered a valuable potential target for cancer research^[1].