Journal of Hepato-Biliary-Pancreatic Sciences

Original Article

Accumulation of phosphorylated p62 is associated with NF-E2-related factor 2 activation in hepatocellular carcinoma

Corresponding Author

Takayuki Shimizu

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

These authors contributed equally to this work.

Correspondence to: Takayuki Shimizu, MD, Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.

e-mail: [email protected]

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Ken-ichi Inoue,

Ken-ichi Inoue

Center for Research Support, Dokkyo Medical University, Tochigi, Mibu, Japan

These authors contributed equally to this work.Search for more papers by this author

Hiroyuki Hachiya,

Hiroyuki Hachiya

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Norisuke Shibuya,

Norisuke Shibuya

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Taku Aoki,

Taku Aoki

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Keiichi Kubota,

Keiichi Kubota

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Takayuki Shimizu,

Corresponding Author

Takayuki Shimizu

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

These authors contributed equally to this work.

Correspondence to: Takayuki Shimizu, MD, Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.

e-mail: [email protected]

Search for more papers by this author

Ken-ichi Inoue,

Ken-ichi Inoue

Center for Research Support, Dokkyo Medical University, Tochigi, Mibu, Japan

These authors contributed equally to this work.Search for more papers by this author

Hiroyuki Hachiya,

Hiroyuki Hachiya

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Norisuke Shibuya,

Norisuke Shibuya

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Taku Aoki,

Taku Aoki

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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Keiichi Kubota,

Keiichi Kubota

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293 Japan

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First published: 31 May 2016

https://doi.org/10.1002/jhbp.364

Citations: 24

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Abstract

Background

Frequent alterations are observed in glucose metabolism in hepatocellular carcinoma (HCC). Activation of various enzymes, including ones involved in the pentose phosphate pathway, by NF-E2-related factor 2 (NRF2), controls redox homeostasis in HCC. However, the mechanisms mediating NRF2 activation remain unclear. Here, we aimed to investigate the correlation between NRF2, Kelch-like ECH-associated protein 1 (KEAP1) syntheses and p62 phosphorylation in HCC.

Methods

Biospecimens were collected from 30 patients with HCC. Protein samples were prepared through subcellular localization. Protein synthesis and phosphorylation were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Statistical correlations among immunoblotting data and clinical features were analyzed using SPSS.

Results

Compared to non-tumor counterpart, phosphorylated p62 was accumulated in HCC (12/30; 40% of patients). Nuclear localization of NRF2 was frequently augmented in HCC (19/30; 63.3%). Statistically, p62 phosphorylation was associated with augmented activation of NRF2 (P = 0.001). Accumulation of p62 per se was moderately associated with NRF2 activation (P = 0.132). Loss of KEAP1 protein, on the other hand, poorly correlated with NRF2 activation (P = 1.000).

Conclusion

In Japanese HCC, NRF2 activation is associated with phosphorylation of p62, but not with KEAP1 status.

References

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Volume23, Issue8

August 2016

Pages 467-471

Accumulation of phosphorylated p62 is associated with NF-E2-related factor 2 activation in hepatocellular carcinoma

Abstract

Background

Methods

Results

Conclusion

References

Citing Literature

References

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Accumulation of phosphorylated p62 is associated with NF-E2-related factor 2 activation in hepatocellular carcinoma

Abstract

Background

Methods

Results

Conclusion

References

Citing Literature

References

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