A-Type Lamins Associated with Aggressive Colorectal Cancer

Cancer Connect

Proteins called A-type lamins appear to indicate the presence of aggressive disease in patients with colorectal cancer. A-type lamins may also play a role in determining treatment options among these patients. These results were recently published in the journal PLoS ONE.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Although standard therapy often involves chemotherapy, particularly among more advanced-stage colorectal cancers, anticancer responses and corresponding survival rates vary widely among patients with this disease. As such, researchers continue to evaluate certain markers that indicate disease characteristics in order to individualize therapeutic approaches.

Researchers from Europe recently conducted a clinical study to evaluate data from tissue collected from patients with colorectal cancer. Specifically, researchers evaluated the presence of A-type lamins in tissue and associated outcomes among patients.

  • Patients who have A-type lamin-expressing cancers have a significantly worse outcome compared with patients whose cancer does not express A-type lamin.
  • A-type lamin was implicated in promoting the movement of cancer cells in the body, as well as their ability to invade areas such as organs.

The researchers concluded: Expression of A-type lamins increases the risk of death from [colorectal cancer]. If confirmed, A-type lamins may play a role in understanding the prognosis of a patient with colorectal cancer and in determining subsequent treatment options.

Reference: Willis N, Cox T, Rahman-Casans S, et al.Lamin A/C is a risk biomarker in colorectal cancer. PloS One. Available at: . Accessed August 2008.

Lamin A/C Is a Risk Biomarker in Colorectal Cancer
Lamin A/C Is a Risk Biomarker in Colorectal Cancer

Background A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a β-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression. Methodology/Principal Findings An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin. Conclusions Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World.

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