Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility

Abstract

BackgroundTransgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo.MethodsIsogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR.ResultsStable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD.ConclusionsIncreases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2105-8) contains supplementary material, which is available to authorized users.

Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling

“…It was proposed that interaction of PLEC with MAPK/ERK pathway occurs due to interaction of PLEC with hemidesmosomal integrin α6β4, ligation of which by PLEC results in the activation of MAPK/ERK pathway48. Besides tubulin and plakins, actin-binding protein TAGLN2 involved with cancer cell motility and metastatic potential was also significantly decreased in HEY Oct4A KD samples49. These observations are consistent with decreased motility and metastatic potential of Oct4A KD cells that we have previously demonstrated27.…”

Transgelin interacts with PARP1 and affects Rho signaling pathway in human colon cancer cells

“…Previously, gene expression profiling identified that over-expression of TAGLN affected the expression of 256 downstream transcripts, which were closely related to cell morphology, migration and invasion [9]. We also found that transgelin had nuclear localization in colon cancer cells [6].…”

“…In addition, we found that up-regulation of transgelin promoted the metastasis of colon cancer cells, while down-regulation substantially decreased the ability of cell invasion and metastasis [6,9,10].…”

“…According to our previous work [9], the relevant cDNA microarray data was obtained using Affymetrix microarray technique. Over-expression of TAGLN in RKO human colon cancer cells led to a total of 256 downstream transcripts that were differentially expressed with at least a 2-fold change (P<0.05).…”

Functions of nuclear actin-binding proteins in human cancer (Review)

“…Additionally, it is revealed that transgelin was located in the cytoplasm and nucleus of colorectal cancer cells (57). Overexpression of transgelin in human colon cancer cells affects the expression of ~250 other transcripts and enhances the metastatic behavior (58). Thus, it is speculated that transgelin is another transcriptional regulator within the ABP family.…”