TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer

Abstract

Circulating tumor cells (CTCs) are important for metastasis in prostate cancer. T-LAK cell-originated protein kinase (TOPK) is highly expressed in cancer cells. Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells. TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice. Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo. TOPK was modulated by the PI3K/PTEN and ERK pathways during the metastasis of prostate cancer. High levels of TOPK in the tumors of patients were correlated with advanced stages of prostate cancer, especially for high-risk patients of Gleason score≥8, PSA>20ng/ml. In summary, TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer.

Impact of a novel biomarker, T‐LAK cell‐originating protein kinase (TOPK) expression on outcome in malignant glioma

“…13 Sun et al 21 also reported that high-level expression of TOPK correlated with advanced stages of prostate cancer. 21 High TOPK expression is also associated with poor OS and PFS in early stages of ovarian cancer. 25 Using Kaplan-Meier analysis, furthermore, Joel et al 19 compared the OS between GBM patients with the highest (30%) and lowest (30%) expression levels of TOPK.…”

“…Their hazard ratio is 2.13 (95%CI, 1.31–3.47) and 4.05 (95%CI, 2.24–7.03), respectively . Sun et al also reported that high‐level expression of TOPK correlated with advanced stages of prostate cancer . High TOPK expression is also associated with poor OS and PFS in early stages of ovarian cancer .…”

“…Thus, Singh et al reported that TOPK expression was also significantly associated with the stage of disease . Furthermore, TOPK expression is closely related to aggressive migratory capacity in prostate and lung cancers . In fact, TOPK transcriptionally activates the promoters of the genes for matrix metalloproteinase (MMP)‐2 and MMP‐9, which in turn play a key role in migration/invasion of tumors .…”

“…17 Furthermore, TOPK expression is closely related to aggressive migratory capacity in prostate and lung cancers. 13,21 In fact, TOPK transcriptionally activates the promoters of the genes for matrix metalloproteinase (MMP)-2 and MMP-9, which in turn play a key role in migration/invasion of tumors. 22 Recent studies concluded that TOPK was positive in about 45% of cells in nonsmall-cell lung carcinoma, and more importantly that TOPK expression was closely related to histological type, lymph node metastasis, and invasion in patients with nonsmall-cell lung cancer, cervical cancer and cervical intraepithelial cancer.…”

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

“…In colorectal cancer, increased levels of TOPK are correlated with high levels of interleukin-8 ( Xiao et al , 2015 ) and with oncogenic KRAS and BRAF mutations ( Zlobec et al , 2010 ). In prostate cancer, high TOPK expression correlates with increased invasiveness and cancer stage ( Sun et al , 2015 ). Conversely, low TOPK expression is predictive of poor prognosis in cholangiocarcinoma patients ( He et al , 2010 ).…”