安普克
前列腺癌
PI3K/AKT/mTOR通路
转移
医学
癌细胞
前列腺
癌症研究
癌症
信号转导
内科学
蛋白激酶A
细胞生物学
生物
磷酸化
作者
Gangyin Zhao,Gabriel Forn‐Cuní,Marvin Scheers,Pier Pieterszoon Lindenbergh,Jie Yin,Quint van Loosen,Leonardo Passarini,Lanpeng Chen,B. Ewa Snaar‐Jagalska
出处
期刊:Cancer Letters
[Elsevier BV]
日期:2024-02-07
卷期号:587: 216657-216657
被引量:8
标识
DOI:10.1016/j.canlet.2024.216657
摘要
Metastatic colonization by circulating cancer cells is a highly inefficient process. To colonize distant organs, disseminating cancer cells must overcome many obstacles in foreign microenvironments, and only a small fraction of them survives this process. How these disseminating cancer cells cope with stress and initiate metastatic process is not fully understood. In this study, we report that the metastatic onset of prostate cancer cells is associated with the dynamic conversion of metabolism signaling pathways governed by the energy sensors AMPK and mTOR. While in circulation in blood flow, the disseminating cancer cells display decreased mTOR and increased AMPK activities that protect them from stress-induced death. However, after metastatic onset, the mTOR-AMPK activities are reversed, enabling mTOR-dependent tumor growth. Suppression of this dynamic conversion by co-targeting of AMPK and mTOR signaling significantly suppresses prostate cancer cell and tumor organoid growth in vitro and experimental metastasis in vivo, suggesting that this can be a therapeutic approach against metastasizing prostate cancer.
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