mTOR Signaling Components in Tumor Mechanobiology

Abstract

Mechanistic target of rapamycin (mTOR) is a central signaling hub that integrates networks of nutrient availability, cellular metabolism, and autophagy in eukaryotic cells. mTOR kinase, along with its upstream regulators and downstream substrates, is upregulated in most human malignancies. At the same time, mechanical forces from the tumor microenvironment and mechanotransduction promote cancer cells’ proliferation, motility, and invasion. mTOR signaling pathway has been recently found on the crossroads of mechanoresponsive-induced signaling cascades to regulate cell growth, invasion, and metastasis in cancer cells. In this review, we examine the emerging association of mTOR signaling components with certain protein tools of tumor mechanobiology. Thereby, we highlight novel mechanisms of mechanotransduction, which regulate tumor progression and invasion, as well as mechanisms related to the therapeutic efficacy of antitumor drugs.

Construction of an oxidative stress-related lncRNAs signature to predict prognosis and the immune response in gastric cancer

“…The canonical Wnt signaling pathway is activated by the mitotic CDK14/cyclin Y complex via phosphorylation of the LRP6 coreceptor, which leads to anti-inflammatory signaling that inhibits tumor growth 42 . Moreover, mTOR is located at the core of tumor-related signaling pathways 43 and plays a key regulatory role in the cell cycle 44 . The importance of mTORC1 in regulating innate and adaptive immunity has been widely recognized; for example, it regulates immune tolerance related to regulatory T cells 45 .…”

Mechanobiology of Colorectal Cancer

“…The response to these mechanical stimuli will be different regarding the cell and the tissue type [34]. Mechanotransduction use several ways to respond to biophysical cues: (i) mechanosensors in the cell membrane (transmembrane receptors, growth factor receptors and proteins that mediate cell-cell adhesion and cell-ECM interactions), (ii) mechanosensitive ion channels, (iii) ECM proteins, (iv) cytoskeleton components, and (v) nuclear structures (involving the chromatin) [5]. Proteins, such as α-catenin, β-catenin, integrins, von Willebrand factor (vWf), talin, vinculin, p130 Crk-associated substrate (Cas), focal adhesion kinase (FAK), and Src kinases, are included in the focal adhesions and adherens junctions [5].…”

“…A deeper understanding of biophysical mechanisms behind biochemical pathways can lead to the development of new therapeutic strategies. For that purpose, it is important to understand the influence of several physical cues, such as: (i) internal forces of the cells; (ii) forces produced by the neighboring cells; (iii) forces coming from interstitial spaces (such as mechanical tension, compression, and hydrostatic pressure); (iv) forces resulting from the alterations of ECM stiffness; (v) shear stress (the parallel force per unit area applied to cell walls) from the fluid flow (such as blood); and (vi) forces from adhesion molecules [5]. Understanding the role of biophysical cues makes it possible to evaluate which biomechanical response will be activated.…”

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

“…Along with the mechanical and topographical cues mentioned in the previous section, the neural environment presents other mechanical cues to neural cells, including physical forces exerted by the neighbouring cells, compression loading, and shear stress caused by cerebrospinal fluid flow ( Gargalionis et al, 2022 ). The process through which cells integrate these mechanical cues is called mechanotransduction and is mediated by specific intramembrane protein structures called mechanosensors ( Gargalionis et al, 2022 ). These, in turn, transduce the stimuli to intracellular adaptor proteins, which can interact with downstream intracellular and nuclear signalling molecules or the actomyosin cytoskeleton.…”