Cytokeratin 19 regulates endoplasmic reticulum stress and inhibits ERp29 expression via p38 MAPK/XBP-1 signaling in breast cancer cells

Bambang, I Fon; Lü, Dan; Li, Huiping; Chiu, Lily-Lily; Lau, Quek Choon; Koay, Evelyn S C; Zhang, Daohai

doi:10.1016/j.yexcr.2009.02.017

Cited by 49 publications

(58 citation statements)

References 40 publications

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“…26. Briefly, cells (1 Â 10 3 per well) were seeded in triplicate in 96-well culture plates and cultured for 4 days at 37 1C in a humidified, 5% CO 2 atmosphere.…”

Section: Cell Proliferation and Cell Cyclementioning

confidence: 99%

“…26 For wound healing assay, monolayer cells at 90-95% confluence were serum starved for 24 h and then carefully wounded using sterilized pipette tips. After removing detached cells, the cells were incubated at 37 1C for 15 h. Wound cells were photographed immediately (t ¼ 0) and after being cultured for 15 h. Quantitative cell migration assays were performed using Cytoselect TM 24-Well Cell Migration Assay (Cell Biolabs, San Diego, CA, USA).…”

Section: Cell Migrationmentioning

confidence: 99%

“…26 Briefly, cells plated on coverslips were fixed with 4% paraformaldehyde (Sigma-Aldrich) for 20 min and permeabilized with 0.1% Triton X-100 for 10 min. The cells were then incubated overnight with primary antibodies against FN or E-cadherin or vimentin at 4 1C, followed by incubation with Alexa Fluor 488-conjugate streptavidin (1:2000, Invitrogen) for 1 h at room temperature.…”

Section: Immunofluorescence and Confocal Microscopymentioning

confidence: 99%

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Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal–epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells

Bambang

Zhou

et al. 2009

Laboratory Investigation

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Endoplasmic reticulum protein 29 (ERp29) is a novel endoplasmic reticulum (ER) secretion factor that facilitates the transport of secretory proteins in the early secretory pathway. Recently, it was found to be overexpressed in several cancers; however, little is known regarding its function in breast cancer progression. In this study, we show that the expression of ERp29 was reduced with tumor progression in clinical specimens of breast cancer, and that overexpression of ERp29 resulted in G 0 /G 1 arrest and inhibited cell proliferation in MDA-MB-231 cells. Importantly, overexpression of ERp29 in MDA-MB-231 cells led to a phenotypic change and mesenchymal-epithelial transition (MET) characterized by cytoskeletal reorganization with loss of stress fibers, reduction of fibronectin (FN), reactivation of epithelial cell marker E-cadherin and loss of mesenchymal cell marker vimentin. Knockdown of ERp29 by shRNA in MCF-7 cells reduced E-cadherin, but increased vimentin expression. Furthermore, ERp29 overexpression in MDA-MB-231 and SKBr3 cells decreased cell migration/invasion and reduced cell transformation, whereas silencing of ERp29 in MCF-7 cells enhanced cell aggressive behavior. Significantly, expression of ERp29 in MDA-MB-231 cells suppressed tumor formation in nude mice by repressing the cell proliferative index (Ki-67 positivity). Transcriptional profiling analysis showed that ERp29 acts as a central regulator by upregulating a group of genes with tumor suppressive function, for example, E-cadherin (CDH1), cyclin-dependent kinase inhibitor (CDKN2B) and spleen tyrosine kinase (SYK), and by downregulating a group of genes that regulate cell proliferation (eg, FN, epidermal growth factor receptor (EGFR) and plasminogen activator receptor (uPAR)). It is noteworthy that ERp29 significantly attenuated the overall ERK cascade, whereas the ratio of p-ERK1 to p-ERK2 was highly increased. Taken together, our results showed that ERp29 is a novel regulator leading to cell growth arrest and cell transition from a proliferative to a quiescent state, and reprogramming molecular portraits to suppress the tumor growth of MDA-MB-231 breast cancer cells.

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“…26. Briefly, cells (1 Â 10 3 per well) were seeded in triplicate in 96-well culture plates and cultured for 4 days at 37 1C in a humidified, 5% CO 2 atmosphere.…”

Section: Cell Proliferation and Cell Cyclementioning

confidence: 99%

Section: Cell Migrationmentioning

confidence: 99%

Section: Immunofluorescence and Confocal Microscopymentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal–epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells

Bambang

Zhou

et al. 2009

Laboratory Investigation

Self Cite

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“…Извест-но, что снижение его экспрессии приводит к нару-шению функции протеасом и изменению степени клеточной пролиферации [11], высокая интенсив-ность которой характерна для плацентарной ткани.…”

Section: результаты и обсуждениеunclassified

“…Повышенно экспресси-руются при ПН белки цитоскелета -виментин, β-тропомиозин и белок эндоплазматического рети-кулума -эндоплазмин. Увеличение их продукции может иметь компенсаторное значение, поскольку первые два принимают участие в формировании клеточной структуры и функционировании цито-скелета [11,14], а эндоплазмин, как молекулярный шаперон, играет важную роль в эндоплазматиче-ском ретикулуме при ядерной сигнализации и се-креции ряда регуляторных белков [15]. Очевидно, что такая направленность динамики этих белков способствует предотвращению развития декомпен-сированной ПН и донашиванию патологической беременности.…”

Section: результаты и обсуждениеunclassified

Post-translational modifications and differential expression of proteins in placental insufficiency

Pogorelova¹,

Gunko²,

Никашина³

et al. 2016

Probl. reprod.

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Morphology, Motility, and Cytoskeletal Architecture of Breast Cancer Cells Depend on Keratin 19 and Substrate

et al. 2020

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Cancer cells gain motility through events that accompany modulation of cell shape and include altered expression of keratins. However, the role of keratins in change of cancer cell architecture is not well understood. Therefore, we ablated the expression of keratin 19 (K19) in breast cancer cells of the MDA-MB-231 cell line and found that cells lacking K19 become more elongated in culture, with morphological reversion toward the parental phenotype upon transduction of KRT19. Also, the number of actin stress fibers and focal adhesions were significantly reduced in KRT19 knockout (KO) cells. The altered morphology of KRT19 KO cells was then characterized quantitatively using digital holographic microscopy (DHM), which not only confirmed the phenotypic change of KRT19 KO cells but also identified that the K19-dependent morphological change is dependent on the substrate type. A new quantitative method of single cell analysis from DHM, via average phase difference maps, facilitated evaluation of K19-substrate interactive effects on cell morphology. When plated on collagen substrate, KRT19 KO cells were less elongated and resembled parental cells. Assessing single cell motility further showed that while KRT19 KO cells moved faster than parental cells on a rigid surface, this increase in motility became abrogated when cells were plated on collagen. Overall, our study suggests that K19 inhibits cell motility by regulating cell shape in a substrate-dependent manner. Thus, this study provides a potential basis for the altered expression of keratins associated with change in cell shape and motility of cancer cells.

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Cytokeratin 19 regulates endoplasmic reticulum stress and inhibits ERp29 expression via p38 MAPK/XBP-1 signaling in breast cancer cells

Cited by 49 publications

References 40 publications

Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal–epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells

Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal–epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells

Post-translational modifications and differential expression of proteins in placental insufficiency

Morphology, Motility, and Cytoskeletal Architecture of Breast Cancer Cells Depend on Keratin 19 and Substrate

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