Signaling Pathways Driving Aberrant Splicing in Cancer Cells

Area of Science:

• Molecular Biology
• Cancer Research
• Epigenetics

Background:

• Aberrant pre-mRNA splicing is a hallmark of cancer, arising from complex molecular interactions.
• Splicing factors (SFs) regulate gene-specific splicing, and their dysregulation contributes to cancer development.
• Oncogenic signaling pathways are key drivers of altered splicing profiles in cancer cells.

Purpose of the Study:

• To review mechanisms linking cancer cell signaling to aberrant splicing.
• To explore how signaling pathways modulate the activity and localization of key splicing factor families (SR proteins and hnRNPs).

Main Methods:

• Review of current literature on cancer signaling pathways and splicing regulation.
• Analysis of how MAPK, PI3K, and Wnt pathways influence splicing factor function.
• Examination of the role of the tumor microenvironment in modulating splicing factor activity.

Main Results:

• Cancer signaling pathways significantly impact SFs by altering their expression levels and post-translational modifications.
• These alterations affect the nuclear-cytoplasmic ratio of SFs, thereby influencing splicing outcomes.
• Specific pathways like MAPK, PI3K, and Wnt, along with tumor microenvironment signals, are implicated in modulating SR proteins and hnRNPs.

Conclusions:

• Cancer cell signaling pathways are critical regulators of pre-mRNA splicing fidelity.
• Targeting these signaling pathways may offer therapeutic strategies to correct aberrant splicing in cancer.
• Understanding the interplay between signaling and splicing factors is crucial for advancing cancer treatment.