Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Bladder cancer is a significant health concern, particularly in males.
• Invasive behavior is a critical factor influencing bladder cancer prognosis.
• Understanding the molecular mechanisms driving cancer invasion is essential for developing effective treatments.

Purpose of the Study:

• To investigate the role of mammalian target of rapamycin complex 2 (mTORC2) in regulating bladder cancer cell migration and invasion.
• To determine if mTORC2 activity correlates with the invasiveness of human bladder cancer.
• To evaluate the therapeutic potential of targeting mTORC2 for bladder cancer treatment.

Main Methods:

• Assessed mTORC2 activity by measuring AKT phosphorylation at Ser473 in human bladder cancer specimens and cell lines.
• Utilized transwell and denudation assays to measure cell migration.
• Evaluated cell invasion through matrigel and human bladder tissue.
• Employed gene silencing of rictor, a key mTORC2 component, to assess its impact on cancer cell behavior.

Main Results:

• mTORC2 activity was approximately 5-fold higher in invasive human bladder cancer compared to non-invasive types.
• Malignant bladder cancer cell lines exhibited higher baseline mTORC2 activity than normal or benign urothelial cells.
• Gene silencing of rictor significantly inhibited bladder cancer cell migration and invasion, reducing Rac1 activation and paxillin phosphorylation.

Conclusions:

• mTORC2 is a central regulator of bladder cancer cell migration and invasion.
• Elevated mTORC2 activity is associated with invasive bladder cancer.
• Targeting mTORC2 presents a promising strategy for neutralizing bladder cancer invasion.