Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression remains largely unknown.
• Esophageal squamous cell carcinoma (ESCC) is a significant global health concern with limited therapeutic options.

Purpose of the Study:

• To evaluate the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells.
• To investigate the molecular mechanisms underlying SLC7A11's role in ESCC progression.

Main Methods:

• Overexpression of SLC7A11 in ESCC tissues was assessed at mRNA and protein levels.
• Esophageal squamous cell carcinoma (ESCC) cells were treated with Erastin to block SLC7A11.
• Immunoprecipitation-mass spectrometry (IP-MS) was used to identify SLC7A11-binding proteins.
• The effects of deubiquitinase inhibitors on SLC7A11 expression were evaluated.

Main Results:

• SLC7A11 was found to be overexpressed in ESCC tissues.
• Blocking SLC7A11 with Erastin suppressed ESCC cell proliferation, colony formation, and ATP levels, while increasing ROS production.
• Sixty-three SLC7A11-binding proteins were identified, enriched in pathways including spliceosome and ribosome.
• Deubiquitinase inhibitors reduced SLC7A11 protein expression, with PR-619 and GRL0617 showing suppressive effects on cell viability and colony formation.
• Erastin downregulated GPX4, DHODH, β-catenin, p-STAT3, and IL-6 in ESCC cells.

Conclusions:

• SLC7A11 is overexpressed in ESCC and contributes to its malignant phenotypes.
• Blocking SLC7A11 with Erastin mitigates ESCC progression by downregulating key ferroptosis-associated molecules.
• Targeting SLC7A11 presents a potential therapeutic strategy for esophageal squamous cell carcinoma that warrants further investigation.