Amino acid metabolic reprogramming in tumor metastatic colonization

Abstract

Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs. How cancer cells acquire the ability to colonize in distant organs has always been the focus of tumor biology. To enable survival and growth in the new environment, metastases commonly reprogram their metabolic states and therefore display different metabolic properties and preferences compared with the primary lesions. For different microenvironments in various colonization sites, cancer cells must transfer to specific metabolic states to colonize in different distant organs, which provides the possibility of evaluating metastasis tendency by tumor metabolic states. Amino acids provide crucial precursors for many biosynthesis and play an essential role in cancer metastasis. Evidence has proved the hyperactivation of several amino acid biosynthetic pathways in metastatic cancer cells, including glutamine, serine, glycine, branched chain amino acids (BCAAs), proline, and asparagine metabolism. The reprogramming of amino acid metabolism can orchestrate energy supply, redox homeostasis, and other metabolism-associated pathways during cancer metastasis. Here, we review the role and function of amino acid metabolic reprogramming in cancer cells colonizing in common metastatic organs, including lung, liver, brain, peritoneum, and bone. In addition, we summarize the current biomarker identification and drug development of cancer metastasis under the amino acid metabolism reprogramming, and discuss the possibility and prospect of targeting organ-specific metastasis for cancer treatment.

Targeting glutamate metabolism in chronic lung diseases

“…Increased levels of glutamate contribute to cell survival, proliferation and migration. 66,67 Glutamate serves as a precursor for the prominent intracellular antioxidant glutathione, facilitating the maintenance of redox homeostasis within the cell. Increased glutamate uptake could help cystine uptake and glutathione synthesis, thereby promoting lung tumours.…”

“…70 Due to the significant role of glutamate metabolism in cellular growth and functioning, a diverse range of pharmaceutical agents have been formulated to disrupt intracellular glutamate metabolism, aiming to address various diseases. 67 The system Xc− is considered a potential target for small-cell lung cancer treatment. 71 Knocking out system Xc− renders cancer cells sensitive to oxidative stress, reducing lung metastasis of cancer cells.…”

“…Glutamate can provide energy through certain metabolic pathways to meet the growth and metabolic needs of lung cancer cells. Increased levels of glutamate contribute to cell survival, proliferation and migration 66,67 . Glutamate serves as a precursor for the prominent intracellular antioxidant glutathione, facilitating the maintenance of redox homeostasis within the cell.…”

“…Survival of lung squamous cell carcinoma also depends on both glucose and glutamine metabolism 70 . Due to the significant role of glutamate metabolism in cellular growth and functioning, a diverse range of pharmaceutical agents have been formulated to disrupt intracellular glutamate metabolism, aiming to address various diseases 67 . The system Xc− is considered a potential target for small‐cell lung cancer treatment 71 .…”

Nanotechnology‐Empowered Combination Cancer Immunotherapies: Mechanisms, Synergies, and Perspectives

“…Such techniques not only improve therapeutic efficacy, but also help to establish immune memory and reduce the risk of tumor recurrence. [48] The combination of acoustic sensitizers with immune adjuvants or immune checkpoint inhibitors in nanosystems through rational design can achieve synergy between sonodynamic therapy and immunotherapy. For instance, Lei et al developed a small molecule linking the photosensitizer methylene blue with the immune adjuvant imiquimod (R837) via GSH.…”