Correlation between telomerase and mTOR pathway in cancer stem cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Stem Cell Research

Background:

• Cancer stem cells (CSCs) possess self-renewal and differentiation capabilities, making them key therapeutic targets.
• The mammalian target of rapamycin (mTOR) pathway regulates CSC proliferation and self-renewal.
• Human telomerase reverse transcriptase (hTERT) activation confers immortality and stemness to CSCs, correlating with telomerase activity.

Purpose of the Study:

• To investigate the correlation between mTOR and hTERT in CSCs.
• To explore the potential of combined mTOR and hTERT inhibition as a cancer therapy strategy.
• To evaluate the impact of targeting these pathways on CSC self-renewal and drug resistance.

Main Methods:

• The study focuses on the regulatory role of mTOR in telomerase activity at translational and post-translational levels.
• Investigated the effect of mTOR inhibitor rapamycin on telomerase activity.
• Examined the link between the PI3K/AKT/mTOR pathway, hTERT up-regulation, and CSC stemness/drug resistance.

Main Results:

• mTOR inhibition by rapamycin reduces telomerase activity without affecting hTERT mRNA levels.
• A significant correlation exists between mTOR and hTERT, crucial for cancer cell survival and immortality.
• The PI3K/AKT/mTOR pathway and hTERT up-regulation are associated with CSC stemness and drug resistance.

Conclusions:

• Combined inhibition of mTOR and hTERT presents a promising novel strategy for targeting CSCs.
• This dual-targeting approach may exert a synergistic effect on telomerase activity.
• Inhibiting the PI3K/AKT/mTOR pathway and hTERT activation could block CSC self-renewal and overcome drug resistance, paving the way for new cancer therapeutics.