Can changing the amount of transgelin in colorectal cancer cells alter their ability to spread in mice?

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Transgelin is an actin-binding protein that promotes movement in normal cells. Its role in cancer is controversial, although several studies have linked higher levels to more aggressive tumor behavior, advanced stage, and poorer prognosis. This study sought more direct evidence by testing whether experimentally changing transgelin levels in colorectal cancer (CRC) cells altered their metastatic potential in vivo.

The researchers used isogenic CRC cell lines that differed in transgelin expression. They assessed growth and invasiveness with in vitro assays and experimental metastasis with a mouse tail vein assay. They also investigated downstream effects of transgelin overexpression using gene expression profiling and quantitative PCR.

In RKO cells, which have low endogenous transgelin levels, stable overexpression increased invasiveness, growth at low density, and growth in soft agar. It also increased the number and size of lung metastases in the mouse tail vein injection model. Conversely, reducing transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model.

Analysis of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts. Genes affecting the function of actin or other cytoskeletal proteins were over-represented among these changes. HOOK1, SDCCAG8, ENAH/Mena, and TNS1 increased, while EMB, BCL11B, and PTPRD decreased.

The researchers concluded that increasing and decreasing transgelin levels have opposite effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression also influences steady-state mRNA levels for metastasis-related genes.