PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

Pseudopodium-enriched atypical kinase 1 (PEAK1) has been reported to be upregulated in human malignancies and is correlated with a poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is unclear. We investigated PEAK1 expression in breast cancer and analyzed the relationship with clinicopathological status and chemotherapy resistance. We also investigated the role of PEAK1 in breast cancer cells in vitro and in vivo. Immunohistochemistry for PEAK1 was performed in 112 surgically resected breast cancer tissues. The association between clinicopathological status, chemotherapy resistance and PEAK1 expression was determined. The effect of PEAK1 overexpression or downregulation on proliferation, colony formation, invasion, migration, metastasis and doxorubicin sensitivity in MCF-7 cells in vitro and in vivo was studied. PEAK1 was overexpressed in breast cancer tissues. High PEAK1 expression was correlated with tumor size, high tumor grade, tumor stage, lymph node metastasis, recurrence, Ki-67 expression, Her-2 expression and chemotherapy resistance. Inhibiting PEAK1 decreased cell growth, invasion, metastasis and reversed chemoresistance to doxorubicin in breast cancer cells both in vitro and in vivo. High PEAK1 expression was associated with the invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 inhibited cell growth and metastasis and reversed chemoresistance in breast cancer cells. Targeting PEAK1 could be an effective treatment strategy for breast cancer.