Lamin A/C: Function in Normal and Tumor Cells

Abstract

This review is focused on lamin A/C, a nuclear protein with multiple functions in normal and diseased cells. Its functions, as known to date, are summarized. This summary includes its role in maintaining a cell's structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere protection. As lamin A/C has a variety of critical roles within the cell, mutations of the lamin A/C gene and incorrect processing of the protein results in a wide variety of diseases, ranging from striated muscle disorders to accelerated aging diseases. These diseases, collectively termed laminopathies, are also touched upon. Finally, we review the existing evidence of lamin A/C's deregulation in cancer. Lamin A/C deregulation leads to various traits, including genomic instability and increased tolerance to mechanical insult, which can lead to more aggressive cancer and poorer prognosis. As lamin A/C's expression in specific cancers varies widely, currently known lamin A/C expression in various cancers is reviewed. Additionally, Lamin A/C's potential as a biomarker in various cancers and as an aid in more accurately diagnosing intermediate Gleason score prostate cancers is also discussed.

Keywords: cancer; genomic instability; lamin A/C; lamin proteins; nuclear lamina; prostate cancer; tumor cells.

Figure 1

Model of known Lamin A/C functions in normal and diseased cells. (a) A-type lamin’s location and binding partners within the nucleus in normal cells. (b) Effect of low/absent lamin A/C on a cell, including crescent-shaped nuclear morphology caused by the microtubule organizing center (MTOC) pushing into the nucleus [30].