Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer

Autor: Wei Jiunn Lee, Yi Chieh Yang, Yung Wei Lin, Michael Hsiao, Ming Hsien Chien, Min Che Tung, Yu Ching Wen, Ke Fan Pan, Kuo Tai Hua, Chih Ying Chu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Carcinogenesis
Cell
Mice
SCID
Metastasis
Prostate cancer
0302 clinical medicine
N-Terminal Acetyltransferase E
Neoplasm Metastasis
N-Terminal Acetyltransferase A
Cancer
Feedback
Physiological
Protein Stability
lcsh:Cytology
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
030220 oncology & carcinogenesis
Androgens
Disease Progression
ADAM9
Immunology
Biology
Models
Biological
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
DU145
Cell Line
Tumor
medicine
Animals
Humans
Cell migration
Neoplasm Invasiveness
Castration
lcsh:QH573-671
Clonogenic assay
Cell Proliferation
Membrane Proteins
Prostatic Neoplasms
Cell Biology
medicine.disease
Clone Cells
Androgen receptor
ADAM Proteins
Disease Models
Animal
030104 developmental biology
Protein Biosynthesis
Cancer research
Zdroj: Cell Death and Disease, Vol 11, Iss 7, Pp 1-16 (2020)
Cell Death & Disease
ISSN: 2041-4889
DOI: 10.1038/s41419-020-02786-2
Popis: N-α-Acetyltransferase 10 protein (Naa10p) was reported to be an oncoprotein in androgen-dependent prostate cancer (PCa; ADPC) through binding and increasing transcriptional activity of the androgen receptor (AR). PCa usually progresses from an androgen-dependent to an androgen-independent stage, leading to an increase in the metastatic potential and an incurable malignancy. At present, the role of Naa10p in androgen-independent prostate cancer (AIPC) remains unclear. In this study, in silico and immunohistochemistry analyses showed that Naa10 transcripts or the Naa10p protein were more highly expressed in primary and metastatic PCa cancer tissues compared to adjacent normal tissues and non-metastatic cancer tissues, respectively. Knockdown and overexpression of Naa10p in AIPC cells (DU145 and PC-3M), respectively, led to decreased and increased cell clonogenic and invasive abilities in vitro as well as tumor growth and metastasis in AIPC xenografts. From the protease array screening, we identified a disintegrin and metalloprotease 9 (ADAM9) as a potential target of Naa10p, which was responsible for the Naa10p-induced invasion of AIPC cells. Naa10p can form a complex with ADAM9 to maintain ADAM9 protein stability and promote AIPC’s invasive ability which were independent of its acetyltransferase activity. In contrast to the Naa10p-ADAM9 axis, ADAM9 exerted positive feedback regulation on Naa10p to modulate progression of AIPC in vitro and in vivo. Taken together, for the first time, our results reveal a novel cross-talk between Naa10p and ADAM9 in regulating the progression of AIPC. Disruption of Naa10p–ADAM9 interactions may be a potential intervention for AIPC therapy.
Databáze: OpenAIRE
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