IGF2BP1/3 have been reported to promote tumor cell survival, prol

IGF2BP1/3 have been reported to promote tumor cell survival, proliferation, anchorage-independent growth, chemo-resistance and tumor cell invasiveness in vitro. In agreement, an upregulated expression of IGF2BPs has been correlated with an overall poor prognosis and metastasis in various cancers ( Table 2). The review of recent literature suggests that IGF2BP3 synergizes selleck chemicals with HMGA2 in enhancing tumor cell aggressiveness. By preventing miRNA attack, IGF2BP3 was proposed to promote the expression of HMGA2 [16]. Notably, a similar mechanism was proposed for IGF2BP1, which enhances

BTRC1 expression by antagonizing miRNA-dependent degradation of BTRC1 transcripts [130]. These findings support the view, that both proteins serve essential roles in promoting the expression of oncogenic factors by shielding these from being degraded by tumor-suppressive miRNAs.

In addition, IGF2BPs Selleckchem GSK2118436 promote the expression of other oncogenic transcriptional regulators like MYC and LEF1 [36] and [64], again two transcripts targeted by tumor-suppressive miRNAs. Thus it is tempting to speculate that IGF2BP1/3 enhance or sustain ‘oncogenic’ reprogramming of transcription at the post-transcriptional level. Moreover, the target transcripts identified, for instance HMGA2, and the expression signatures of IGF2BP1/3, for instance in the hematopoietic system, suggest that both factors sustain a stemness-like cell phenotype (reviewed in: [1]). This is consistent

with reports on a role of IGF2BP1 in modulating stemness-like cell properties during development and the strikingly upregulated expression of IGF2BPs in aggressive and thus frequently de-differentiated cancers (reviewed in: [1]). In addition to promoting a stemness-like tumor cell phenotype, IGF2BP1/3 were also shown to promote the migratory and invasive potential of tumor cells L-NAME HCl in vitro. We propose, that this is mainly facilitated by IGF2BP1, which has been shown to modulate actin dynamics, pro-migratory adhesion, tumor cell invasiveness and was reported to induce metastasis in a transgenic mouse model [36], [37], [38], [39] and [46]. Evidence for a pro-invasive role of IGF2BP3 is mainly based on loss-of-function studies yet downstream effectors remain largely elusive or require further validation. Moreover, the only to date reported mouse model does not support an oncogenic nor pro-metastatic role of the protein [47]. In conclusion, we propose that IGF2BP1 and IGF2BP3 present potent post-transcriptional oncogenes, which enhance tumor cell aggressiveness.

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