Abstract
The extracellular matrix (ECM) is a complex network of secreted proteins which provides support for tissues and organs. Additionally, the ECM controls a plethora of cell functions, including cell polarity, migration, proliferation, and oncogenic transformation. One of the hallmarks of cancer is altered cell metabolism, which is currently being exploited to develop anti-cancer therapies. Several pieces of evidence indicate that the tumor microenvironment and the ECM impinge on tumor cell metabolism. Therefore, it is essential to understand the contribution of the complex 3D microenvironment in controlling metabolic plasticity and responsiveness to therapies targeting cell metabolism. In this mini-review, we will describe how the tumor microenvironment and cancer-associated fibroblasts dictate cancer cell metabolism, resulting in increased tumor progression. Moreover, we will define the cross-talk between nutrient signaling and the trafficking of the ECM receptors of the integrin family. Finally, we will present recent data highlighting the contribution of nutrient scavenging from the microenvironment to support cancer cells growth under nutrient starvation conditions.
Highlights
Cancer-associated fibroblasts (CAFs) are a heterogenous and plastic population of activated fibroblasts, which represent a significant proportion of the tumor microenvironment
CAFs play an important role in the regulation of cancer metabolism, primarily through the secretion of metabolites and the generation of a stiffer and fibrotic extracellular matrix (ECM), which in turn affects cancer cell metabolism
Even though studies on mTORC1 activity suggest that nutrient deficiency assist cells to benefit from alternative food sources such as fibronectin and laminin through receptor dependent-endocytosis, this study shows that starvation could have an inhibitory effect on integrin membrane transport and trafficking
Summary
Biomedical Science Department, The University of Sheffield, Sheffield, United Kingdom. Specialty section: This article was submitted to Cancer Metabolism, a section of the journal
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