ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer

Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong‐Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang‐Gu; An, Sungkwan; Han, Young‐Hoon; Kim, Jae-Sung

doi:10.18632/oncotarget.3042

Cited by 54 publications

(66 citation statements)

References 44 publications

(82 reference statements)

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“…These findings may be the supportive evidence that PDIA3 functions mainly through the STAT3 signaling pathway. These results are consistent with those from several cancer cell lines (18,19), suggesting that PDIA3 is involved in the phosphorylation process and the DNA-binding activity of STAT3. Furthermore, an association was observed between PDIA3 and P-STAT3 expression in HCC tissues.…”

Section: Discussionsupporting

confidence: 91%

“…In several types of cancer, PDIA3 forms a complex with STAT3 in the nucleus (16)(17)(18). A high frequency of PDIA3-STAT3 complex formation is a marker of poor prognosis and increases resistance to radiotherapy in laryngeal cancer through modulation of STAT3 activity (19). We have previously reported that the PDIA3 expression levels in HCC tissues are higher than those in adjacent non-cancerous tissues, and that they are associated with overall survival time (20).…”

Section: Downregulation Of Protein Disulfide-isomerase A3 Expression mentioning

confidence: 99%

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Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

et al. 2019

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Protein disulfide-isomerase A3 (PDIA3) is a chaperone protein that modulates folding of newly synthesized glycoproteins and responds to endoplasmic reticulum (ER) stress. Previous studies reported that increased expression of PDIA3 in hepatocellular carcinoma (HCC) is a marker for poor prognosis. However, the mechanism remains poorly understood. The aim of the present study, therefore, was to understand the role of PDIA3 in HCC development. First, immunohistochemical staining of tissues from 53 HCC cases revealed that HCC tissues with high PDIA3 expression exhibited a higher proliferation index and contained fewer apoptotic cells than those with low expression. In addition, the knockdown of PDIA3 significantly inhibited cell proliferation and induced apoptosis in HCC cell lines. These results suggest that PDIA3 regulates cell proliferation and apoptosis in HCC. An examination of whether PDIA3 knockdown induced apoptosis through ER stress revealed that PDIA3 knockdown did not increase ER stress marker, 78 kDa glucose-regulated protein, in HCC cell lines. Furthermore, the association between PDIA3 and the signal transducer and activator of transcription 3 (STAT3) signaling pathway were investigated in vitro and in vivo. Immunofluorescence staining and co-immunoprecipitation experiments revealed colocalization and binding, respectively, of PDIA3 and STAT3 in HCC cell lines. The knockdown of PDIA3 decreased the levels of phosphorylated STAT3 (P-STAT3; Tyr705) and downstream proteins of the STAT3 signaling pathway: The anti-apoptotic proteins (Bcl-2-like protein 1, induced myeloid leukemia cell differentiation protein Mcl-1, survivin and X-linked inhibitor of apoptosis protein). In addition, PDIA3 knockdown provided little inhibitory effect on cell proliferation in HCC cell lines treated with AG490, a tyrosine-protein kinase JAK/STAT3 signaling inhibitor. Finally, an association was demonstrated between PDIA3 and P-STAT3 expression following immunostaining of 35 HCC samples. Together, the present data suggest that PDIA3 promotes HCC progression through the STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Section: Downregulation Of Protein Disulfide-isomerase A3 Expression mentioning

confidence: 99%

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

et al. 2019

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“…28 Suppression of the ERp57-STAT3 pathway is necessary to enhance the efficacy of radiotherapy in human laryngeal cancer. 29 In lung adenocarcinoma study, we found that the levels of STAT3/p-STAT3 were higher in irradiation-induced A549/R34 cells than in A549 cells. Knockdown of STAT3 by miR-320a significantly increased the apoptosis of A549/R34 cells induced by irradiation in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 77%

MiR-320a effectively suppresses lung adenocarcinoma cell proliferation and metastasis by regulating STAT3 signals

et al. 2017

Cancer Biology & Therapy

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MicroRNAs play important roles in tumorigenesis of various types of cancers. MiR-320a can inhibits cell proliferation of some cancers, but the biologic roles of miR-320a in lung cancer need to be further studied. Here, we investigated the roles of miR-320a in suppressing the proliferation of lung adenocarcinoma cells. MiR-320a treatment was found to effectively suppress LTEP-a-2 and A549 cell proliferation, and induce more apoptotic cells with irradiation treatment compared with control treatment. Our results also showed that miR-320a, as a novel miRNA, directly regulated signal transducer and activator of transcription 3 (STAT3) and its signals, such as Bcl ¡ 2, Bax, and Caspase 3. The siRNA-inhibited STAT3 levels further proved its roles in regulating STAT3 signals. Moreover, miR-320a treatment effectively suppressed cancer cell growth in mice xenografts compared with controls, and significantly inhibited cell migration in vitro and in vivo. Our findings collectively demonstrated that miR-320a, by directly regulating STAT3 signals, not only suppressed cell proliferation and metastasis, but also enhanced irradiation-induced apoptosis of adenocarcinomia cells.Abbreviations: GFP, green fluorescent protein; HE, hematoxylin-eosin staining; miRNAs, microRNAs; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NSCLC, Non-small cell lung cancer; STAT3, signal transducer and activator of transcription 3

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“…73 ERp57 is associated with tumor progression ans has been described to modulate STAT 3 activity, thus regulating radioresistance in laryngeal cancer. 74 Accordingly, ERp57 has been described as a poor prognosis factor.…”

Section: Dna Damage Repair Biomarkersmentioning

confidence: 99%

A genetic view of laryngeal cancer heterogeneity

2016

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During the recent decades significant improvements in the understanding of laryngeal molecular biology allowed a better characterization of the tumor. However, despite increased molecular knowledge and clinical efforts, survival of patients with laryngeal cancer remains the same as 30 years ago. Although this result may not make major conclusions as preservation approaches were not broadly used until the time of database collection, it seems to be clear that there is still window for improvement.

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ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer

Cited by 54 publications

References 44 publications

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

MiR-320a effectively suppresses lung adenocarcinoma cell proliferation and metastasis by regulating STAT3 signals

A genetic view of laryngeal cancer heterogeneity

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