Nuclear αvβ3 integrin expression, post translational modifications and regulation in hematological malignancies

Area of Science:

• Hematology
• Cell Biology
• Oncology

Background:

• αvβ3 integrin is a plasma membrane protein found on many tumors.
• Nuclear αvβ3 integrin has been observed in ovarian cancer cells.

Purpose of the Study:

• To investigate the presence and function of nuclear αvβ3 integrin in T-cell acute lymphoblastic leukemia (T-ALL) and Mast cell leukemia (MCL).
• To examine nuclear αvβ3 integrin in primary chronic lymphocytic leukemia (CLL) cells and normal B cells.

Main Methods:

• Western blots, confocal microscopy, and ImageStream technology were used to detect nuclear αvβ3 integrin.
• Post-translational modifications, nuclear trafficking, and protein interactions (Co-immunoprecipitation) were analyzed.
• Inhibitors of MAPK and PI3K pathways were used to study nuclear trafficking regulation.

Main Results:

• Nuclear αvβ3 integrin was identified in all tested leukemia and CLL cell models and is N-glycosylated.
• Inhibition of MAPK and PI3K pathways increased nuclear αvβ3 integrin levels and decreased membrane levels.
• Nuclear αvβ3 integrin interacts with ERK, Histone H3, and Lamin B1 in T-ALL cells, and Histone H3 in CLL cells.

Conclusions:

• This study identifies nuclear αvβ3 integrin in hematological malignancies.
• The findings suggest novel, potentially membrane-independent, cancer-relevant functions of nuclear αvβ3 integrin.