Ribosome biogenesis and cancer: basic and translational challenges
Section snippets
Alterations of RiBi pathways in cancer
Mounting evidence has underscored the implication of RiBi in cancer cells. However, the molecular mechanisms that contribute to the deregulation of this process only have begun to be understood in recent years. Perhaps not surprisingly, current findings indicate that one of the most common RiBi regulatory points targeted in cancer cells is the RNA polymerase I (POL I) complex itself. This is a logical interference point since this enzyme is involved in the key rate-limiting step of this
Potential roles of RiBi in cancer
The foregoing data prompt the question of the actual role of RiBi in cancer cells. In the case of RiBi hyperactivity, the most straightforward explanation is that this process favors the increased rates of protein synthesis usually supported by cancer cells. This interpretation is consistent with old findings indicating that translation initiation and elongation factors can facilitate cell transformation (see R. Schneider's review, in this issue). However, it is important to note that the
RiBi-associated therapeutic opportunities
It is widely assumed that RiBi can represent a pharmacologically amenable Achilles’ heel for many tumors, namely those commonly associated with highly increased RiBi rates. This has led to the development of POL I inhibitors with demonstrated antitumor activity such as CX-5461 and BMH-21 [48, 49]. However, it cannot be ruled out that the antitumoral action of these compounds is due to either off-target or indirect effects on POL I. For example, the cytotoxic effects of CX-5461 have recently
Concluding remarks and future perspectives
Despite the progress described above, many lingering problems still remain. One of the main hurdles that preclude further progress in the field is the limited information that still exists on the organization of the RiBi pathway in human cells. Indeed, the molecular details of many steps of the human route, the functions of most human-specific RiBi factors, and the changes that take place in ribosome biogenesis in different cell types, tissues, and physiological conditions remain largely
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The authors would like to apologize to researchers not cited in this work due to space limitations. Work in XRB lab is supported by grants from the Castilla-León Government (BIO/SA01/15, CSI049U16), the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2015-64556-R, RD12/0036/0002), Worldwide Cancer Research (14-1248), Ramón Areces Foundation, and Spanish Society Against Cancer. Work in MD lab is supported by a MINECO grant (BFU2014-52729-P). Spanish funding is partially cosponsored
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2022, Journal of Biological ChemistryCitation Excerpt :The basic cell functional machineries such as the cell cycle, ribosomes, proteasomes, spliceosomes, and epigenetic modifications have been proven to play active roles during tumorigenesis. Inhibition of the activity of these machineries either has been applied to cancer therapy or is under evaluation in preclinical trials (43–51). Considering the contribution of neural stemness to cell tumorigenicity and the similarity in the regulatory network between cancer cells and NSCs (1, 11, 13), inhibition of cancer via targeted therapy is per se achieved by disruption of the neural regulatory network.
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2021, Translational ResearchCitation Excerpt :By depleting the RPs cargo in the MM-MSCs MVs and cancelling their pro-MM effect we reinforced this understanding. It is readily understood how increased ribosome biogenesis contributes to intensive protein synthesis needed by cancer cells yet accumulating data indicate that RPs may introduce competitive advantages by modifying cellular proteome as well, particularly in cancer.37 Acquired aberrations in RPs have been described in glioma, colorectal cancers, chronic lymphocytic leukemia, and T-cell acute lymphoblastic leukemia (mutations and/or biogenesis).38