How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

Peckham, Michelle

doi:10.1042/bst20160034

Cited by 32 publications

(26 citation statements)

References 109 publications

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“…Modifications of the actin cytoskeleton during the metastatic process are well described (Vignjevic & Montagnac, 2008;Nürnberg et al, 2011;Peckham, 2016). Notably the relative amount of filamentous actin (F-actin) and monomeric actin (G-actin), which indicates the level of actin polymerisation, depends on the cell malignancy.…”

Section: Actinmentioning

confidence: 99%

Are cancer cells really softer than normal cells?

Charlotte

Goud

Manneville

2017

Biology of the Cell

279

236

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Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression.

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Section: Actinmentioning

confidence: 99%

Are cancer cells really softer than normal cells?

Charlotte

Goud

Manneville

2017

Biology of the Cell

279

236

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“…This property first appeared in ancient MyTH4-FERM myosins and is conserved over 1 billion y of evolution (14,16,17). Mutations of MyTH4-FERM myosins cause a broad spectrum of human diseases, including hearing loss, vision defects, digestive disorders, and cancers (18)(19)(20)(21), often because of defects in actin bundle-supported protrusions (i.e., filopodia, microvilli, or stereocilia). The specific functions of Myo7a, Myo7b, Myo10, and Myo15a in regulating actin-bundle protrusion structures in various tissues must be a result of, at least in part, the unique cargo binding properties of their MyTH4-FERM domains.…”

mentioning

confidence: 99%

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

Weck

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.M icrovilli and stereocilia are both actin bundle-based, fingerlike protrusions found on apical surfaces of many epithelial cells (1). Microvilli line the apical surface of epithelial cells forming a densely packed structure known as the brush border in tube-like tissues, such as intestines, kidney, and lung (2-5). The best known function of microvilli is to massively increase membrane surface area of these tissues to promote solute exchange, although these protrusions may also allow cells to communicate with their extracellular surroundings (6). Stereocilia, on the other hand, are composed of several rows of protrusions with graded height forming a staircase-like structure on the apical surface of inner ear hair cells, which collectively function to sense sound waves (7,8). Despite clear morphological and functional differences, microvilli and stereocilia share certain features at the molecular level. For example, the packing and organization of microvilli and stereocilia both rely on homologous cadherin-based tip-link complexes that target to the distal ends of these protrusions (9, 10). Additionally, a set of homologous unconventional myosins-including Myo1, Myo3, Myo6, and Myo7-are shared by and critical for the development, maintenance, and functions of microvilli and stereocilia (1,11,12).This study focuses on Myo7b, an unconventional myosin enriched in the microvilli of transporting epithelial cells (11, 13). Myo7b is characterized by a pair of MyTH4-FERM tandems in its tail cargo-binding domain. In addition to Myo7b, Myo7a, Myo10, and Myo15a also contain one or two MyTH4-FERM tandems in their tail domains (14). A common property of MyTH4-FERM myosins is their involvement in the formation or elongation/stabilization of actin-bundle support...

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“…GO and KEGG pathway enrichment analysis shows that these PMPs were mainly enriched in actin lament organization. Studies have found that actin lament organization plays a role in a variety of tumors such as prostate cancer, head and neck cancers and melanomas [11]. However, there is no reports about actin lament organization in renal cancer, further experimental exploration is needed in the future.…”

Section: Discussionmentioning

confidence: 99%

A plasma membrane protein based prognostic model in clear cell renal cell carcinoma

Liu

Fang

Liu

et al. 2020

Preprint

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Background Renal cell cacinoma (RCC) accounts for 3% of human cancers, and clear cell renal cell carcinoma (ccRCC) is the most common pathological type of RCC. Cell surface proteins have been shown to play an important role in the occurrence and progression of various cancers. In this study, we focused on plasma membrane proteins (PMPs), to explore their potential value in ccRCC. Methods The PMPs expression profiles and ccRCC patients’ clinical information were downloaded from TCGA database. Through a series of bioinformatic methods, we established a plasma membrane proteins prognostic model. Results Multivariate cox regression analysis and area under receiver operating characteristic curve indicated that this model was an effective independent predictor of ccRCC clinical outcomes. Combined with other two clinical characteristics, a nomogram was constructed to predict patient survival at 1, 3, and 5 years. Conclusions Our study is the first to explore the prognostic value of plasma membrane proteins in clear cell renal cell carcinoma. We hope our work could provide a new viewpoint for ccRCC prognosis and drawn people’s attention to plasma membrane proteins in clear cell renal cell carcinoma.

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How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

Cited by 32 publications

References 109 publications

Are cancer cells really softer than normal cells?

Are cancer cells really softer than normal cells?

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

A plasma membrane protein based prognostic model in clear cell renal cell carcinoma

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