Phosphorylated Heat Shock Protein 20 (HSPB6) Regulates Transforming Growth Factor-α-Induced Migration and Invasion of Hepatocellular Carcinoma Cells

Matsushima‐Nishiwaki, Rie; Toyoda, Hidenori; Nagasawa, Takayuki; Yasuda, Eisuke; Chiba, Naokazu; Okuda, Seiji; Maeda, Atsuyuki; Kikuchi, Yuji; Kumada, Takashi; Kozawa, Osamu

doi:10.1371/journal.pone.0151907

Cited by 30 publications

(42 citation statements)

References 38 publications

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“…Whereas HSPB4 seems to restrain cell migration and to negatively regulate pancreatic carcinogenesis, HSPB5 induces epidermal growth factor (EGF)-independent growth and increases cell migration and invasion (Deng et al 2010;Moyano et al 2006). HSPB6 has been recently shown to regulate transforming growth factor-α (TGF-α)-induced migration and invasion of hepatocellular carcinoma cells (Matsushima-Nishiwaki et al 2016). Interestingly, a phospho-HSPB6 mimetic reduces their invasive potential, illustrating the importance of sHSPs' post-translational modifications.…”

Section: Shsps In Cancermentioning

confidence: 99%

Small heat shock proteins in ageing and age-related diseases

Charmpilas

Kyriakakis

Tavernarakis

2017

Cell Stress and Chaperones

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Small heat shock proteins (sHSPs) are gatekeepers of cellular homeostasis across species, preserving proteome integrity under stressful conditions. Nonetheless, recent evidence suggests that sHSPs are more than molecular chaperones with merely auxiliary role. In contrast, sHSPs have emerged as central lifespan determinants, and their malfunction has been associated with the manifestation of neurological disorders, cardiovascular disease and cancer malignancies. In this review, we focus on the role of sHSPs in ageing and ageassociated diseases and highlight the most prominent paradigms, where impairment of sHSP function has been implicated in human pathology.

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Section: Shsps In Cancermentioning

confidence: 99%

Small heat shock proteins in ageing and age-related diseases

Charmpilas

Kyriakakis

Tavernarakis

2017

Cell Stress and Chaperones

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“…In case of humans, the scenario is more complicated, since different sHSPs are present in varying concentrations in different tissues and are expressed in different developmental stages. They are involved in several important functions like maintaining eye lens transparency, protecting the cytoskeletal proteins, facilitating cell signaling etc., and their malfunctioning has been implicated in large number of pathologies . In this regard, it is important to mention that mutation of a conserved arginine (in the ACD) at the dimer interface has been involved in pathologies like cataract and desmin‐related myopathy .…”

Section: Introductionmentioning

confidence: 99%

Dodecameric structure of a small heat shock protein from Mycobacterium marinum M

et al. 2019

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Small heat shock proteins (sHSPs) are ATP‐independent molecular chaperones present ubiquitously in all kingdoms of life. Their low molecular weight subunits associate to form higher order structures. Under conditions of stress, sHSPs prevent aggregation of substrate proteins by undergoing rapid changes in their conformation or stoichiometry. Polydispersity and dynamic nature of these proteins have made structural investigations through crystallography a daunting task. In pathogens like Mycobacteria, sHSPs are immuno‐dominant antigens, enabling survival of the pathogen within the host and contributing to disease persistence. We characterized sHSPs from Mycobacterium marinum M and determined the crystal structure of one of these. The protein crystallized in three different conditions as dodecamers, with dimers arranged in a tetrahedral fashion to form a closed cage‐like architecture. Interestingly, we found a pentapeptide bound to the dodecamers revealing one of the modes of sHSP‐substrate interaction. Further, we have observed that ATP inhibits the chaperoning activity of the protein.

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“…This study group recently demonstrated that TGF-α induced the migration of HuH7 cells via the SAPK/JNK (18) and AKT (19) pathways. Therefore, the present study examined whether or not the ERK, p38 MAPK and Rho kinase pathways were also involved in the TGF-α-induced HuH7 cell migration.…”

Section: Effects Of Pd98059 Sb203580 or Y27632 On Tgf-α-induced Migrmentioning

confidence: 98%

“…A Transwell cell migration assay was performed using a Boyden chamber (polycarbonate membrane with 8 µm pores, Transwell; Costar; Corning, Inc.) as described previously (18,19). Briefly, the cultured cells were seeded (1x10 5 cells/well) onto the upper chamber in serum-free RPMI-1640 medium.…”

Section: Cell Migration Assaymentioning

confidence: 99%

“…Blocking was performed prior to incubation with the primary antibodies using 5% skim milk for 1 h at room temperature. Western blot analyses were performed as described previously (18,19,21) using phospho-specific AKT (T308) (1:1,000), AKT (1:10,000), phospho-specific SAPK/JNK (1:1,000), SAPK/JNK (1:3,000), phospho-specific p38 MAPK (1:20,000), p38 MAPK (1:20,000), phospho-specific MYPT-1 (1:1,000), MYPT-1 (1:1,000) and GAPDH (1:1,000) antibodies with horseradish peroxidase (HRP)-labeled anti-rabbit IgG and anti-mouse IgG antibodies (1:1,000; cat. nos., 7074 and 7076, respectively, Cell Signaling Technology, Inc.) as secondary antibodies.…”

Section: Cell Migration Assaymentioning

confidence: 99%

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Olive oil polyphenols suppress the TGF‑α‑induced migration of hepatocellular carcinoma cells

et al. 2019

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Oleuropein and 3-hydroxytyrosol (3-HT) are natural polyphenols present in olive oil that are known to exhibit potent anti-oxidant activities and exert protective effects against a number of human diseases. In the liver, olive oil polyphenols have been demonstrated to prevent hepatocellular carcinoma (HCC) cell growth. However, little is known about their effects against HCC cell migration. Therefore, the present study investigated whether or not oleuropein and 3-HT were involved in the suppression of transforming growth factor-α (TGF-α)-induced migration of human HCC cells using human HCC-derived HuH7 cells. The TGF-α-induced migration of HuH7 cells was significantly and dose-dependently suppressed by oleuropein and 3-HT. This study group demonstrated previously that the TGF-α-induced activation of AKT and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were involved in HuH7 cell migration. In addition to these protein kinases, the present study examined the involvement of TGF-α-induced activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Rho kinase in HuH7 cell migration. TGF-α-induced HuH7 cell migration was decreased by SB203580, a p38 MAPK inhibitor, and Y27632, a Rho kinase inhibitor. However, PD98059, an inhibitor of the upstream kinase activating ERK, did not suppress the TGF-α-induced migration of HuH7 cells. Although AKT, SAPK/JNK, p38 MAPK and Rho kinase pathways were suggested to be involved in the TGF-α-induced migration of HuH7 cells, 10-30 µM 3-HT did not exhibit any suppressive effect on the TGF-α-stimulated activities of these kinases. The results of the present study suggest that olive oil polyphenols suppressed the TGF-α-induced migration of HCC cells.

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Phosphorylated Heat Shock Protein 20 (HSPB6) Regulates Transforming Growth Factor-α-Induced Migration and Invasion of Hepatocellular Carcinoma Cells

Cited by 30 publications

References 38 publications

Small heat shock proteins in ageing and age-related diseases

Small heat shock proteins in ageing and age-related diseases

Dodecameric structure of a small heat shock protein from Mycobacterium marinum M

Olive oil polyphenols suppress the TGF‑α‑induced migration of hepatocellular carcinoma cells

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