Mitosis can drive cell cannibalism through entosis

Area of Science:

• Cell Biology
• Cancer Research
• Biophysics

Background:

• Entosis, or epithelial cell cannibalism, is common in human cancers and usually triggered by loss of matrix adhesion.
• The role of cell division in entosis has not been well understood.

Purpose of the Study:

• To investigate an alternative mechanism for entosis driven by mitosis in human epithelial cells.
• To explore the regulatory pathways and biophysical changes involved in mitotic entosis.
• To assess the relevance of mitotic entosis in human cancers and its response to chemotherapy.

Main Methods:

• Depletion of Cdc42 to observe effects on mitotic deadhesion and rounding.
• Inhibition of RhoA and Rap1 signaling pathways.
• Analysis of mitotic index and cell cannibalism in human breast tumor samples.
• Treatment of cells with Paclitaxel/taxol.

Main Results:

• Cdc42 depletion enhances mitotic deadhesion and rounding, promoting entosis.
• RhoA activation and Rap1 inhibition phenocopy these biophysical changes.
• Mitotic entosis occurs constitutively in some cancer cell lines, with mitotic index correlating to cell cannibalism in breast tumors.
• Paclitaxel/taxol promotes mitotic rounding and subsequent entosis.

Conclusions:

• Mitosis provides an alternative mechanism for inducing entosis in human epithelial cells.
• Cdc42, RhoA, and Rap1 are key regulators of mitotic entosis.
• Mitotic entosis is relevant in human cancers and normal epithelia, with implications for chemotherapy.