Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells

Lechuga, Susana; Baranwal, Somesh; Li, Chao; Naydenov, Nayden G.; Kuemmerle, John F.; Dugina, Vera B.; Chaponnier, Christine; Ivanov, Andrei I.

doi:10.1091/mbc.e14-03-0815

Cited by 30 publications

(30 citation statements)

References 74 publications

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“…S1). This is supported by observations from other studies where neither isoform knockdown significantly affected the total level of actin in HSCF cells (Dugina et al, ) and A549 human lung epithelial cells (Lechuga, Baranwal, Li, Naydenov, Kuemmerle, Dugina, … Ivanov, ). GBM cells, however, show significantly reduced levels of total actin expression during γ‐CYA knockdown (Supporting Information Fig.…”

Section: Resultssupporting

confidence: 84%

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Divergent roles of β‐ and γ‐actin isoforms during spread of vaccinia virus

et al. 2017

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Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Here we show that virus-tipped actin comets are composed of β- and γ-actin. We employed isoform-specific siRNA knockdown to examine the role of the two isoforms in VACV-induced actin comets. Despite the high level of similarity between the actin isoforms, and their colocalization, VACV-induced actin nucleation was dependent exclusively on β-actin. Knockdown of β-actin led to a reduction in the release of virus from infected cells, a phenotype dependent on virus-induced Arp2/3 complex activity. We suggest that local concentrations of actin isoforms may regulate the activity of cellular actin nucleator complexes.

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Section: Resultssupporting

confidence: 84%

“…S1). This is supported by observations from other studies where neither isoform knockdown significantly affected the total level of actin in HSCF cells (Dugina et al, 2009) and A549 human lung epithelial cells (Lechuga, Baranwal, Li, Naydenov, Kuemmerle, Dugina, . .…”

Section: Band C-sirna Treatment Induces Isoformspecific Knockdown Isupporting

confidence: 85%

Divergent roles of β‐ and γ‐actin isoforms during spread of vaccinia virus

et al. 2017

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“…Embryonic lethality, with γ-cytoplasmic actin null mice ( Actg1 −/−) dead within 48h after birth [ 11 ], complicated the study of non-muscle actin isoforms. Selective siRNA-mediated knockdown of γ-cytoplasmic actin as compared to β-actin, induced epithelial-to-mesenchymal transition of various epithelial cells, which manifested in increased expression of contractile proteins along with inhibition of genes responsible for cell proliferation [ 40 ]. Some data indicated a role of β- and γ-actins in carcinogenesis: components of the Arp2/3 complex were up-regulated in colorectal cancers [ 41 ], increased ACTG1 and reduced ACTB levels were identified in osteosarcoma analysis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Tumor promotion by γ and suppression by β non-muscle actin isoforms

et al. 2015

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Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.

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“…The studies using small interfering RNA (siRNA) reported that knockdown of γ-actin more dramatically impaired motility of human subcutaneous fibroblasts, spontaneously immortalized keratinocytes, and neuroblastoma SHEP cells than did knockdown of β-actin [5,[7][8][9][10] in 2D test systems. It is accepted that the enhanced motility of cancer cells is crucial for invasion.…”

Section: Introductionmentioning

confidence: 99%

Divergent impact of actin isoforms on cell cycle regulation

et al. 2018

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We have shown that cytoplasmic actin isoforms play different roles in neoplastic cell transformation. β-Cytoplasmic actin acts as a tumor suppressor, affecting epithelial differentiation, cell growth, cell invasion and tumor growth of colon and lung carcinoma cells. In contrast, γ-cytoplasmic actin enhances malignant features of tumor cells whose actin network regulation is carried out via the γ-actin isoform. The goal of this study was to describe the role of cytoplasmic actins in cell cycle regulation of breast cancer cell lines MCF-7 and MDA-MB-231. The distinct roles of each cytoplasmic actin in the cell cycle driving were observed. β-Actin as well as γ-actin down-regulation inhibited proliferation of breast cancer cells, but only down-regulation of β-actin induced a significant decrease in diploid cell population and accumulation of tetraploid cells. Down-regulation of β-actin stimulated cyclin A2, B1 and D3 expression, whereas down-regulation of γ-actin reduced expression of these cyclins in both cell lines. Moreover, cyclin B1 and γ-actin were co-localized in mitotic control and β-actin-deficient cells. In mitotic MCF-7 cells down-regulation of β-actin caused an enrichment of prophase/metaphase population compared with control. γ-Actin down-regulation induced telophase enrichment.ERK1/2 and γ-actin co-localization and possible selective binding were revealed in MCF7 cells. β-Actin down-regulation induced ERK1/2 activation, while γ-actin down-regulation led to reduction of p-ERK1/2. A direct interaction of ERK1/2 with γ-actin and cyclin A2 in the same protein complex was also discovered. We suggest that γ-actin down-regulation leads to decrease of cyclin A2 level, inhibits ERK1/2 signaling and deceleration of breast cancer cells proliferation.

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Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells

Cited by 30 publications

References 74 publications

Divergent roles of β‐ and γ‐actin isoforms during spread of vaccinia virus

Divergent roles of β‐ and γ‐actin isoforms during spread of vaccinia virus

Tumor promotion by γ and suppression by β non-muscle actin isoforms

Divergent impact of actin isoforms on cell cycle regulation

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