Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan
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J. Clin. Med. 2019, 8(3), 354; https://doi.org/10.3390/jcm8030354
Received: 20 February 2019 / Revised: 10 March 2019 / Accepted: 11 March 2019 / Published: 13 March 2019
(This article belongs to the Special Issue Cytobiology of Human Prostate Cancer Cells and Its Clinical Applications)
Androgen/androgen receptor (AR) signaling is a significant driver of prostate cancer progression, therefore androgen-deprivation therapy (ADT) is often used as a standard form of treatment for advanced and metastatic prostate cancer patients. However, after several years of ADT, prostate cancer progresses to castration-resistant prostate cancer (CRPC). Androgen/AR signaling is still considered an important factor for prostate cancer cell survival following CRPC progression, while recent studies have reported dichotomic roles for androgen/AR signaling. Androgen/AR signaling increases prostate cancer cell proliferation, while simultaneously inhibiting migration. As a result, ADT can induce prostate cancer metastasis. Several C-C motif ligand (CCL)-receptor (CCR) axes are involved in cancer cell migration related to blockade of androgen/AR signaling. The CCL2-CCR2 axis is negatively regulated by androgen/AR signaling, with the CCL22-CCR4 axis acting as a further downstream mediator, both of which promote prostate cancer cell migration. Furthermore, the CCL5-CCR5 axis inhibits androgen/AR signaling as an upstream mediator. CCL4 is involved in prostate carcinogenesis through macrophage AR signaling, while the CCL21-CCR7 axis in prostate cancer cells is activated by tumor necrotic factor, which is secreted when androgen/AR signaling is inhibited. Finally, the CCL2-CCR2 axis has recently been demonstrated to be a key contributor to cabazitaxel resistance in CRPC.
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Keywords:
prostate cancer; androgen receptor; castration-resistant prostate cancer; CCL2; CCL22; CCL5; migration
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MDPI and ACS Style
Izumi, K.; Mizokami, A. Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells. J. Clin. Med. 2019, 8, 354. https://doi.org/10.3390/jcm8030354
AMA Style
Izumi K, Mizokami A. Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells. Journal of Clinical Medicine. 2019; 8(3):354. https://doi.org/10.3390/jcm8030354
Chicago/Turabian StyleIzumi, Kouji; Mizokami, Atsushi. 2019. "Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells" J. Clin. Med. 8, no. 3: 354. https://doi.org/10.3390/jcm8030354
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