Simultaneous targeting of AMPK and mTOR is a novel therapeutic strategy against prostate cancer

Area of Science:

• Oncology
• Metabolism
• Cell Biology

Background:

• Metastatic colonization is inefficient, with few circulating tumor cells surviving to form secondary tumors.
• The metabolic adaptations of disseminating cancer cells to survive and initiate metastasis remain unclear.

Purpose of the Study:

• To investigate the role of metabolic signaling pathways, specifically AMPK and mTOR, in prostate cancer cell metastasis.
• To explore the dynamic conversion of these pathways during metastatic onset and its therapeutic implications.

Main Methods:

• Analysis of AMPK and mTOR activity in circulating and established prostate cancer cells.
• In vitro and in vivo experiments assessing the impact of targeting AMPK and mTOR signaling on cancer cell growth and metastasis.
• Utilized prostate cancer cell lines and tumor organoids for experimental models.

Main Results:

• Circulating prostate cancer cells exhibit decreased mTOR and increased AMPK activity, conferring stress resistance.
• Upon metastatic colonization, this activity is reversed, with increased mTOR promoting tumor growth.
• Co-targeting AMPK and mTOR signaling suppressed prostate cancer cell and tumor organoid growth and reduced experimental metastasis.

Conclusions:

• The dynamic conversion of AMPK and mTOR signaling is critical for prostate cancer cell survival during circulation and subsequent metastatic growth.
• Targeting both AMPK and mTOR pathways represents a potential therapeutic strategy to inhibit prostate cancer metastasis.