A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis

Goldenring, James R.

doi:10.1038/nrc3601

Cited by 145 publications

(150 citation statements)

References 112 publications

(114 reference statements)

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“…The role of internal membranes, molecular crowding, or active force generators in the cytoplasm is less documented but could also be significant. During cancer development, signaling associated to the cytoskeleton as well as membrane trafficking, cell polarity, and intracellular organization are deregulated (14)(15)(16), supporting the idea that the mechanics of the interior of cancer cells could differ from that of normal cells.…”

mentioning

confidence: 67%

Mapping intracellular mechanics on micropatterned substrates

Mandal

Asnacios

Goud

et al. 2016

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

116

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The mechanical properties of cells impact on their architecture, their migration, intracellular trafficking, and many other cellular functions and have been shown to be modified during cancer progression. We have developed an approach to map the intracellular mechanical properties of living cells by combining micropatterning and optical tweezers-based active microrheology. We optically trap micrometersized beads internalized in cells plated on crossbow-shaped adhesive micropatterns and track their displacement following a step displacement of the cell. The local intracellular complex shear modulus is measured from the relaxation of the bead position assuming that the intracellular microenvironment of the bead obeys power-law rheology. We also analyze the data with a standard viscoelastic model and compare with the power-law approach. We show that the shear modulus decreases from the cell center to the periphery and from the cell rear to the front along the polarity axis of the micropattern. We use a variety of inhibitors to quantify the spatial contribution of the cytoskeleton, intracellular membranes, and ATPdependent active forces to intracellular mechanics and apply our technique to differentiate normal and cancer cells.ell mechanics play a crucial role in many cellular functions that are critical during development or are altered during pathologies such as cancers. For instance, cell migration, cell adhesion, and cell division have all been shown to depend on cell mechanics (1-5). Most studies have focused on the mechanical cross talk between the cell and its microenvironment at the whole-cell or the tissue level. It has been shown recently that intracellular mechanics could also be used to differentiate cancer cells from normal cells (6-9). Several intracellular elements participate in the mechanical response of the cytoplasm, and most of them may be modified during cancer progression. The three types of fibers constituting the cytoskeleton, actin, microtubules, and intermediate filaments, clearly contribute to cell mechanics (10-13). The role of internal membranes, molecular crowding, or active force generators in the cytoplasm is less documented but could also be significant. During cancer development, signaling associated to the cytoskeleton as well as membrane trafficking, cell polarity, and intracellular organization are deregulated (14-16), supporting the idea that the mechanics of the interior of cancer cells could differ from that of normal cells.Passive or active microrheology techniques have been developed to measure intracellular mechanical properties, mostly based on the tracking of endogenous granules or internalized particles (17)(18)(19)(20)(21)(22). The experimental results are generally analyzed using two main classes of models, viscoelastic models with a finite number of viscous (dashpots) and elastic (springs) elements and power-law (PL) models (see refs. 23-26 for reviews). An increasing amount of experimental evidence points to weak PL rheology as a common feature of cell mechanical res...

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mentioning

confidence: 67%

Mapping intracellular mechanics on micropatterned substrates

Mandal

Asnacios

Goud

et al. 2016

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

116

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“…In addition to genetic mutations, dysregulation of Rab GTPases is also observed in cancers (Table 2). Typically, increased expression levels of certain Rab GTPases, such as Rab1a, Rab3a, Rab5a or Rab7a, are associated with progression of specific cancer types, although there are also examples suggesting that loss of Rab expression can drive cancers, as shown for Rab25 in colon cancer (Goldenring, 2013). An example of how increased Rab expression might drive cancer progression is provided by Rab5a, which is overexpressed in aggressive breast cancers.…”

Section: Rab Gtpases and Diseasesmentioning

confidence: 99%

“…Interestingly, mutations in the gene encoding the Rab27a effector Breast cancer, gastric cancer Jacob et al, 2013;Li et al, 2015 In general, these Rab GTPases are overexpressed in cancers. The exception is Rab25, whose expression is decreased in triple-negative breast cancer, colon cancer and head and neck cancer (Goldenring, 2013 Effector for Rab8a and Rab11a…”

Section: Rab Gtpases and Diseasesmentioning

confidence: 99%

Cellular functions of Rab GTPases at a glance

Zhen

Stenmark

2015

Journal of Cell Science

340

328

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Rab GTPases control intracellular membrane traffic by recruiting specific effector proteins to restricted membranes in a GTPdependent manner. In this Cell Science at a Glance and the accompanying poster, we highlight the regulation of Rab GTPases by proteins that control their membrane association and activation state, and provide an overview of the cellular processes that are regulated by Rab GTPases and their effectors, including protein sorting, vesicle motility and vesicle tethering. We also discuss the physiological importance of Rab GTPases and provide examples of diseases caused by their dysfunctions.

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“…Vesicle-mediated transport of intracellular proteins drives the formation of actin-based membrane projections such as lamellipodia and filopodia and the secretion of extracellular matrix-modifying factors that facilitate angiogenesis and tumor cell invasion (1). Vesicle transport is regulated by the Golgi apparatus, which posttranslationally modifies, sorts, and packages proteins into vesicles that bud from the Golgi and are transported along microtubules to specific intracellular locations (2).…”

Section: Introductionmentioning

confidence: 99%