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Abstract
Simple SummaryCancer is the second leading cause of death worldwide, right after cardiovascular diseases, and the invasion and metastatization correspond to the foremost cause of cancer-related deaths. Here, we reviewed the state of the art regarding the importance of HOX transcription factors in these last steps of cancer progression and described five of their complex mechanisms of regulation, including the miRs and lncRNAs interference. This information highlights the importance of HOX in the suppression and induction of disease advancement and point out the potential of HOX products as therapeutic targets for diverse cancer types.Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra- and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.
Highlights
The vast majority of cancer-related mortality in solid tumours is associated with the capacity of the cancer cells to invade and colonize nearby or distant vital organs forming metastasis [1], hallmarks that characterize the last steps of cancer progression [2]
HOX proteins interfere with invasion and metastasis of cancer cells due to their ability to affect the expression of TGFβ genes, which are multifunctional cytokines secreted by different cells, with important roles in embryonic development controlling cell behaviour, namely cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration [61]
Invasion and metastasis are the leading causes of cancer-related death, as they reflect the last stages of cancer
Summary
The vast majority of cancer-related mortality in solid tumours is associated with the capacity of the cancer cells to invade and colonize nearby or distant vital organs forming metastasis [1], hallmarks that characterize the last steps of cancer progression [2]. A line of investigation suggests that tumour recurrence and metastization is led by a population of residual cells that survive treatment and are capable to leave their primary location These cells disperse into the bloodstream, endure pressure in blood vessels, escape immune response, and acclimate to new cellular surroundings in a secondary site [3]. The genetic modifications involve changes in the primary DNA sequence, such as mutations, while the epigenetic mechanisms relate to chemical modifications of DNA bases and changes in the chromosomal superstructure in which DNA is packaged, such as gene promoter methylations associated with gene silencing [12,13] In this context, alterations in HOX gene expression have been identified in primary tumours, metastasis and CTCs [14,15]
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