The tumor suppressor p53 can promote collective cellular migration

Area of Science:

• Cell Biology
• Cancer Research
• Biophysics

Background:

• The tumor suppressor p53 is crucial in cellular processes.
• Loss of p53 function is linked to increased cell migration in Boyden chamber assays.

Purpose of the Study:

• To investigate the role of p53 in cellular migration within 2D confluent layers and 3D multicellular spheroids.
• To determine if the effect of p53 on migration is consistent across different cellular microenvironments.

Main Methods:

• Utilized two human carcinoma cell lines: EJ (bladder) and HCT116 (colorectal).
• Assessed cell migration, speed, diffusion coefficients, actin organization, cell polarity, traction forces, and lamellipodia formation in 2D and 3D models.
• Compared p53-null cells with p53-expressing cells.

Main Results:

• In 2D confluent layers, p53-null cells showed significantly reduced migratory speeds and diffusion coefficients compared to p53-expressing cells.
• Loss of p53 led to more organized cortical actin rings, reduced front-rear polarity, smaller substrate traction forces, and decreased cryptic lamellipodia formation.
• In 3D spheroids, p53-null cells exhibited reduced collective migration into the surrounding collagen matrix.

Conclusions:

• The impact of p53 on cellular migration is highly context-dependent.
• Extrapolation of p53's role in migration from traditional assays like the Boyden chamber to other microenvironments is unreliable.
• These findings reveal a paradoxical role of p53 in cell migration, differing significantly from established knowledge.