Mechanical tumor microenvironment and transduction: cytoskeleton mediates cancer cell invasion and metastasis

Li, Xingchen; Wang, Jianliu

doi:10.7150/ijbs.44943

Cited by 123 publications

(82 citation statements)

References 192 publications

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“…Previous studies also found that TRPV4 regulated the thickness of F-actin stress fibers and the reinforcement of focal adhesion contacted through TRPV4-induced cation/calcium influx 50 . Many signaling pathways have been reported to have an impact on cytoskeletal regulation through metastasis including RhoA/ROCK, PI3K/mTOR, and Hippo pathway 51 . In this research, we focused on the RhoA/ROCK1 pathway and cytoskeletal regulation.…”

Section: Discussionmentioning

confidence: 99%

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

Cheng

Wang

et al. 2020

Cell Death Dis

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Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway. We reported here on the findings that a high level of serum ionized calcium was significantly correlated with advanced EC progression, and among all the calcium channels, TRPV4 played an essential role, with high levels of TRPV4 expression associated with cancer progression both in vitro and in vivo. Proteomic and bioinformatics analysis revealed that TRPV4 was involved in cytoskeleton regulation and Rho protein pathway, which regulated EC cell migration. Mechanistic investigation demonstrated that TRPV4 and calcium influx acted on the cytoskeleton via the RhoA/ROCK1 pathway, ending with LIMK/cofilin activation, which had an impact on F-actin and paxillin (PXN) levels. Overall, our findings indicated that ionized serum calcium level was significantly associated with poor outcomes and calcium channel TRPV4 should be targeted to improve therapeutic and preventive strategies in EC.

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Section: Discussionmentioning

confidence: 99%

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

Cheng

Wang

et al. 2020

Cell Death Dis

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“…The functional consequences of oncogenic mutations of KRAS , p53 and APC in CRC involve marked alterations of the actin cytoskeleton [ 13 , 14 , 15 ]. Furthermore, the abnormal structure and dynamics of actin filaments could be induced by altered physical properties and increased proinflammatory signaling of the tumor stroma [ 12 , 16 , 17 , 18 ]. Such a complex interplay between autonomous and extrinsic factors in the cell creates significant challenges for understanding the mechanisms and functional consequences of the altered actin cytoskeletal organization in CRC.…”

Section: Introductionmentioning

confidence: 99%

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Naydenov

Lechuga

Huang

et al. 2021

Cancers

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Colorectal cancer (CRC) remains the third most common cause of cancer and the second most common cause of cancer deaths worldwide. Clinicians are largely faced with advanced and metastatic disease for which few interventions are available. One poorly understood aspect of CRC involves altered organization of the actin cytoskeleton, especially at the metastatic stage of the disease. Myosin motors are crucial regulators of actin cytoskeletal architecture and remodeling. They act as mechanosensors of the tumor environments and control key cellular processes linked to oncogenesis, including cell division, extracellular matrix adhesion and tissue invasion. Different myosins play either oncogenic or tumor suppressor roles in breast, lung and prostate cancer; however, little is known about their functions in CRC. This review focuses on the functional roles of myosins in colon cancer development. We discuss the most studied class of myosins, class II (conventional) myosins, as well as several classes (I, V, VI, X and XVIII) of unconventional myosins that have been linked to CRC development. Altered expression and mutations of these motors in clinical tumor samples and their roles in CRC growth and metastasis are described. We also evaluate the potential of using small molecular modulators of myosin activity to develop novel anticancer therapies.

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“…In these processes, cytoskeleton remodeling plays an important role [ 136 ]. External signals are received from mechanosensors and translated into internal responses by the cytoskeleton, activating different pathways such as the Hippo pathway, the focal adhesion kinases (FAK), GTP-binding protein RhoA, and JAK/STAT [ 137 ].…”

Section: Inter-organellar Communications In Cancer Cellsmentioning

confidence: 99%

“The Loss of Golden Touch”: Mitochondria-Organelle Interactions, Metabolism, and Cancer

Audano

Pedretti

Ligorio

et al. 2020

Cells

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Mitochondria represent the energy hub of cells and their function is under the constant influence of their tethering with other subcellular organelles. Mitochondria interact with the endoplasmic reticulum, lysosomes, cytoskeleton, peroxisomes, and nucleus in several ways, ranging from signal transduction, vesicle transport, and membrane contact sites, to regulate energy metabolism, biosynthetic processes, apoptosis, and cell turnover. Tumorigenesis is often associated with mitochondrial dysfunction, which could likely be the result of an altered interaction with different cell organelles or structures. The purpose of the present review is to provide an updated overview of the links between inter-organellar communications and interactions and metabolism in cancer cells, with a focus on mitochondria. The very recent publication of several reviews on these aspects testifies the great interest in the area. Here, we aim at (1) summarizing recent evidence supporting that the metabolic rewiring and adaptation observed in tumors deeply affect organelle dynamics and cellular functions and vice versa; (2) discussing insights on the underlying mechanisms, when available; and (3) critically presenting the gaps in the field that need to be filled, for a comprehensive understanding of tumor cells’ biology. Chemo-resistance and druggable vulnerabilities of cancer cells related to the aspects mentioned above is also outlined.

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Mechanical tumor microenvironment and transduction: cytoskeleton mediates cancer cell invasion and metastasis

Cited by 123 publications

References 192 publications

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

“The Loss of Golden Touch”: Mitochondria-Organelle Interactions, Metabolism, and Cancer

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