FLRT2 suppresses bladder cancer progression through inducing ferroptosis.

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Bladder cancer is a prevalent malignancy with a poor prognosis.
• The role of Fibronectin leucine rich transmembrane protein 2 (FLRT2) in bladder cancer pathogenesis is not well understood.

Purpose of the Study:

• To investigate the function of FLRT2 in human bladder cancer.
• To elucidate the molecular mechanisms underlying FLRT2's role in bladder cancer.

Main Methods:

• Analysis of FLRT2 expression levels in human bladder cancer tissues.
• In vitro studies involving FLRT2 overexpression and silence in bladder cancer cell lines.
• Investigation of downstream targets and cellular processes, including lipid peroxidation and ferroptosis.

Main Results:

• FLRT2 expression is reduced in human bladder cancer tissues.
• Higher FLRT2 levels are associated with a lower survival rate.
• FLRT2 overexpression inhibited tumor cell growth, migration, and invasion.
• FLRT2 silence promoted tumor cell proliferation, migration, and invasion.
• FLRT2 upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) expression.
• FLRT2 promotes lipid peroxidation and induces ferroptosis in bladder cancer cells.

Conclusions:

• FLRT2 functions as a tumor suppressor gene in bladder cancer.
• FLRT2 inhibits bladder cancer progression by elevating ACSL4 expression, increasing lipid peroxidation, and triggering ferroptosis.