Ribosome and Cancer

The ribosome is an important cellular organelle for the translation of the information in mRNA into various functional proteins. Dysregulation of its biogenesis is inextricably linked to spontaneous cancer. The investigation of the molecular mechanism of ribosome biogenesis in cancer is now providing opportunities for designing new targeted cancer therapeutics. With years of experience in advanced biotechnology, Creative Biolabs provides global customers with diverse ribosome-related separation, extraction, and analysis services.

The Role of Ribosome in Cancer

The ribosome consists of a variety of proteins and nucleic acids. It is responsible for translating mRNA information into functional proteins. Ribosome biogenesis involves several hundred accessory factors, and the ribosome function is coordinated by multiple cellular signals. The genesis and progression of spontaneous cancers are influenced by ribosome biogenesis dysregulation, which can be caused by the deletion of oncogenes or tumor suppressor genes, resulting in excessive ribosome activation. Mutations in genes encoding ribosomal proteins (RPs) or ribosome assembly components have been linked to the formation of sporadic human cancers. The molecular mechanism of ribosome biogenesis in cancer will provide opportunities to design new targeted therapeutics for cancer, such as drugs that inhibit ribosome biogenesis. Monitoring ribosome biogenesis, quality control mechanisms, and cellular checkpoints will establish the foundation for the development of novel targeted anti-cancer therapeutics.

Dysregulated Ribosome Biogenesis in Cancer

The cause of cancers related to the ribosome is divided into hyperactive ribosome biogenesis and qualitative ribosome alterations.

Hyperactivation of RNA polymerase I (Pol I)-dependent transcription and ribosome biogenesis appears to increase global protein synthesis rates and might reduce translational fidelity or change the translated mRNAs, and thus potentially leading to cancer initiation and progression. Those signaling and proteins related to hyperactivated ribosome biogenesis include nucleolar N-terminal truncated isoform of netrin 1 (ΔN-netrin-1), epithelial cell-transforming sequence 2 oncogene (ECT2), AKT–mTOR complex 1 (mTORC1) signaling and MYC proto-oncogene protein. On the contrary, Nucleomethylin (NML) and fibroblast growth factor 13 (FGF13) signaling play a role in downregulating the Pol I transcription. They reduce ribosome biogenesis, which decreases proliferation.

Ribosomal qualitative changes, such as loss of ribosomal protein (RP) genes, missense mutation in RP genes, RP genes paralogue exchange, and rRNA modifications, could be degraded by the quality control mechanism, that reduce the global protein synthesis rates, potentially contributing to cancer.

Fig.1 Dysregulated ribosome biogenesis in cancer. (Pelletier, 2017)

Therapeutic Opportunities

Hyperactive ribosome biogenesis is detrimental to normal cell growth and survival due to cellular proteotoxic stress and energetic stress. Several protective mechanisms are established to prevent and solve the hyperactive ribosome biogenesis-caused cellular challenges, including Antimetabolites and DNA-damaging agents, protein kinase Cι (PKCι) inhibitors, Pol I inhibitors, Translation inhibitors, Proteasome or AAA ATPase p97 (p97) inhibitors, and mTOR inhibitors. Through a comprehensive understanding of the molecular mechanism of ribosomes, we can further explore the association between ribosomes and cancer, and discover more possibilities for cancer therapeutic solutions.

To learn more about ribosomes and cancer, please check out the following links:

• Ribosome Related Cancer
• Ribosome Biogenesis and Cancer development
• Ribosome Biogenesis and Neoplastic Transformation

Creative Biolabs has an experienced and professional team that would offer a variety of ribosome-related services to our global clients, providing integrated coverage for cancer treatment solutions. Following are some related services:

• Ribosome Separation and Extraction Services
• Ribosome Analysis Services
• Ribosomal Marker Antibody Development Services

Please do not hesitate to contact us.

Reference

1. Pelletier, J.; et al. Ribosome biogenesis in cancer: new players and therapeutic avenues. Nature Reviews Cancer. 2018,18(1), 51-63.