Journal
EBIOMEDICINE
Volume 82, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2022.104155
Keywords
APPLI; AURKB; Cancer; Mitosis; T beta RI; TRAF6
Funding
- Swedish Medical Research Council [2019-01598, 2015-02757, 2020-01291]
- Swedish Cancer Society [20 0964]
- Umea University
- Region Vasterbotten (ALF) [RV939377, 967041, 970057]
- European Research Council [787472]
- Kempe Foundation [SMK-1866]
- National Microscopy Infrastructure [NMI VR-RFI 2016-00968]
- Vinnova [2019-01598] Funding Source: Vinnova
- Swedish Research Council [2020-01291, 2015-02757, 2019-01598] Funding Source: Swedish Research Council
- Forte [2020-01291] Funding Source: Forte
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This study found that AURKB-TβRI complexes are formed during mitosis and cytokinesis in prostate cancer cells and neuroblastoma cells. The study also suggests that AURKB-TβRI complexes are correlated with the malignancy of prostate cancer in tumor tissue of patients.
Background Transforming growth factor beta (TGF beta) is overexpressed in several advanced cancer types and promotes tumor progression. We have reported that the intracellular domain (ICD) of TGF beta receptor (T beta R) I is cleaved by proteolytic enzymes in cancer cells, and then translocated to the nucleus in a manner dependent on the endosomal adaptor proteins APPLI/2, driving an invasiveness program. How cancer cells evade TGF beta-induced growth inhibition is unclear. Methods We performed microarray analysis to search for genes regulated by APPLI/2 proteins in castration-resistant prostate cancer (CRPC) cells. We investigated the role of TBR beta and TRAF6 in mitosis in cancer cell lines cultured in 10% FBS in the absence of exogenous TGF beta. The molecular mechanism of the ubiquitination of AURKB by TRAF6 in mitosis and the formation of AURKB-T beta RI complex in cancer cell lines and tissue microarrays was also studied. Findings During mitosis and cytokinesis, AURKB-T beta RI complexes formed in midbodies in CRPC and KELLY neuroblastoma cells. TRAF6 induced polyubiquitination of AURKB on K85 and K87, protruding on the surface of AURKB to facilitate its activation. AURKB-T beta RI complexes in patient's tumor tissue sections correlated with the malignancy of prostate cancer. Interpretation The AURKB-T beta RI complex may become a prognostic biomarker for patients with risk of developing aggressive PC. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.
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