Aberrant expression of katanin p60 in prostate cancer bone metastasis

Abstract

BACKGROUND Katanin p60 is a microtubule-severing protein and is involved in microtubule cytoskeleton organization in both mitotic and non-mitotic processes. Its role in cancer metastasis is unknown. METHODS Differential protein profiles of bone marrow aspirates were analyzed by chromatography, electropheresis and mass spectrometry. Expression of katanin p60 in primary and metastatic prostate cancer was examined by immunohistochemistry. Cellular function of katanin p60 was further examined in prostate cell lines. RESULTS In a proteomic profiling of bone marrow aspirates from men with prostate cancer, we found that katanin p60 was one of the proteins differentially expressed in bone metastasis samples. Immunohistochemical staining showed that katanin p60 was expressed in the basal cells in normal human prostate glands. In prostatic adenocarcinomas, in which the basal cells were absent, katanin p60 was expressed in the prostate cancer cells. In the specimens from bone metastasis, katanin p60 was detectable in the metastatic cancer cells. Strikingly, some of the metastatic cancer cells also co-expressed basal cell biomarkers including the tumor suppressor p53-homologous protein p63 and the high molecular weight cytokeratins, suggesting that the metastatic prostate cancer cells may have a basal cell-like phenotype. Moreover, overexpression of katanin p60 inhibited prostate cancer cell proliferation but enhanced cell migration activity. CONCLUSIONS Katanin p60 was aberrantly expressed during prostate cancer progression. Its expression in the metastatic cells in bone was associated with the re-emergence of a basal cell-like phenotype. The elevated katanin p60 expression may contribute to cancer cell metastasis via a stimulatory effect on cell motility.

Katanin P80 correlates with larger tumor size, lymph node metastasis, and advanced TNM stage and predicts poor prognosis in non–small‐cell lung cancer patients

“…16 Previous studies have revealed the role of katanin P60 in the initiation and development of several cancers. [17][18][19] For example, one study illustrates that katanin P60 is highly expressed in breast cancer bone metastatic tissues compared with primary tumor tissues, and its overexpression promotes cell migration but inhibits cell proliferation in breast cancer, suggesting the important role of katanin P60 in breast cancer metastasis. 17 Another study investigates the association of katanin P60 with clinicopathological features and survival profile in breast cancer patients, which demonstrates that katanin P60 positive expression is correlated with higher lymph node metastasis, and its high expression independently predicted worse prognosis in breast cancer patients.…”

“…18 In addition, katanin P60 is aberrantly expressed during the prostate cancer progression, and its overexpression is responsible for cancer cell metastasis via promoting cell motility in prostate cancer. 19 Regarding katanin P80, as another subunit of katanin, it is also involved in the microtubule remodeling through microtubule-severing activities and is of important value in regulation of various cell processes, including cellular homeostasis, proliferation, and invasion during meiosis and mitosis. 12,20 With regard to its role in tumorigenesis, there are only two related studies available.…”

Engagement of DYRK2 in proper control for cell division

“…Surprisingly, prostate cancer cells that highly express Katanin p60 showed a high migration ability, but also an inhibition of cell proliferation. 26 Because DYRK2 expression declined in prostate cancer tissues, 8 DYRK2 might inhibit cell migration via Katanin p60 degradation in prostatic adenocarcinomas.…”

Models, Regulations, and Functions of Microtubule Severing by Katanin

“…Few studies are revealing altered Katanin functioning in modulation of diseases. Expression and functional pattern of Katanin p60 subunit in prostate cancer show variability when compared to normal prostate [ 64 ]. Higher expression of p60 in prostate cancer causes inhibition of cell proliferation but allows cancerous cells to take more aggressive migration property.…”

“…In normal prostates, expression of p60 is only limited in basal cells while in prostate adenocarcinoma cells, p60 expression is much higher throughout prostate. Role of Katanin in metastasis is presumed to be mediated by enhanced microtubule severing activity which enforces reorganization of cytoskeleton structure to help forming cellular protrusions involved in cell motility [ 64 , 65 ]. Higher p60 expression is also observed in bone metastatic cells.…”