bims-mecami 2024-08-04 papers

Issue of 2024–08–04
three papers selected by
Oltea Sampetrean, Keio University

Cell Commun Signal. 2024 Jul 29. 22(1): 380

The significant role of amino acid metabolic reprogramming in cancer.

Xiaohong Liu, Bo Ren, Jie Ren, Minzhi Gu, Lei You, Yupei Zhao.

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can influence the behavior of stromal cells, such as cancer-associated fibroblasts, regulate ECM remodeling and promote angiogenesis, thereby facilitating tumor growth and metastasis. Understanding the intricate interplay between amino acid metabolism and the tumor microenvironment is of crucial significance. Expanding our knowledge of the multifaceted roles of amino acid metabolism in tumor microenvironment holds significant promise for the development of more effective cancer therapies aimed at disrupting the metabolic dependencies of cancer cells and modulating the tumor microenvironment to enhance anti-tumor immune responses and inhibit tumor progression.

Keywords: Amino acid metabolism; Angiogenesis; Epigenetic regulation; Immune tolerance; Redox; Tumor microenvironment

DOI: https://doi.org/10.1186/s12964-024-01760-1

Cancer Res. 2024 Jul 02. 84(13): 2046-2048

The Warburg Effect Revisited through Blood and Electron Flow.

Yahui Wang, Chi V Dang.

The Warburg effect describes the propensity of many cancers to consume glucose avidly and convert it to lactate in the presence of oxygen. The benefit of the Warburg effect on cancer cells remains enigmatic, particularly because extracellular disposal of incompletely oxidized lactate is wasteful. However, lactate is not discarded from the body, but rather recycled as pyruvate for metabolism through the tricarboxylic acid cycle in oxidative tissues and cells. Hence, tissue and interorgan metabolism play important roles in tumor metabolism. The production of tumor lactate to be recycled elsewhere parallels the Cori cycle, in which lactate produced by muscle activity is shuttled to the liver, where it is converted to pyruvate and subsequently stored as glucose moieties in glycogen. This perspective will consider this organismal contextwhile discussing how glucose is used in tumors. We highlight several key articles published decades ago in Cancer Research that are foundational to our current understanding of cancer biology and metabolism.

DOI: https://doi.org/10.1158/0008-5472.CAN-24-0474

Adv Sci (Weinh). 2024 Jul 31. e2309966

Extracellular Matrix Sulfation in the Tumor Microenvironment Stimulates Cancer Stemness and Invasiveness.

Tumor extracellular matrices (ECM) exhibit aberrant changes in composition and mechanics compared to normal tissues. Proteoglycans (PG) are vital regulators of cellular signaling in the ECM with the ability to modulate receptor tyrosine kinase (RTK) activation via their sulfated glycosaminoglycan (sGAG) side chains. However, their role on tumor cell behavior is controversial. Here, it is demonstrated that PGs are heavily expressed in lung adenocarcinoma (LUAD) patients in correlation with invasive phenotype and poor prognosis. A bioengineered human lung tumor model that recapitulates the increase of sGAGs in tumors in an organotypic matrix with independent control of stiffness, viscoelasticity, ligand density, and porosity, is developed. This model reveals that increased sulfation stimulates extensive proliferation, epithelial-mesenchymal transition (EMT), and stemness in cancer cells. The focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signaling axis is identified as a mediator of sulfation-induced molecular changes in cells upon activation of a distinct set of RTKs within tumor-mimetic hydrogels. The study shows that the transcriptomic landscape of tumor cells in response to increased sulfation resembles native PG-rich patient tumors by employing integrative omics and network modeling approaches.

Keywords: cancer; extracellular matrix (ECM); hydrogels; tissue engineering; tumor microenvironment (TME); tumor models

DOI: https://doi.org/10.1002/advs.202309966