RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44⁺ cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
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