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The roles of PKCs in regulating autophagy

Abstract

Purpose

Autophagy, as a highly conserved cellular degradation and recycling process, plays an important part in maintaining cellular homeostasis. PKC signaling is involved in multiple pathways including cell cycle progression, tumorigenesis, migration and autophagy.

Methods

Literatures about PKC and autophagy from PubMed databases were reviewed in this study.

Results

Studies regarding the association of PKC and autophagy remain debatable. Different duration of the stimulation of autophagy and distinct cell contexts result in different function of PKC in regulating autophagy. The subcellular localization of PKCs and their downstream regulators may influence the autophagy regulation as well. As important intracellular components, the mitochondria play an important role in regulating autophagy, by metabolic modulation and structural derangement.

Conclusion

Phase II studies regarding PKC-β inhibitor, enzastaurin, showed promising results in MCL, DLBCL and recurrent high-grade gliomas. However, the detailed mechanism is still in need. The mechanism of PKC-β in mediating autophagy in lymphoma and high-grade gliomas remains elusive as well. Moreover, several studies were in agreement that rottlerin enhanced autophagy in breast cancer cells, which warrants further clinical studies to verify PKC-δ as a therapeutic target. Thus, identifying the function of PKC in modulating autophagy and conducting related clinical studies help find novel target for chemotherapy.

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Acknowledgements

We are grateful to the staff at the NHC Key Laboratory of Radiobiology (Ministry of Health).

Funding

This study was supported by National Natural Science Foundation of China (NSFC) grants [grant number 31500682].

Author information

Correspondence to Lili Jia.

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Conflict of interest

Tianyi Wang declares that he has no conflict of interest. Conghe Liu declares that she has no conflict of interest. Lili Jia declares that she has no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Wang, T., Liu, C. & Jia, L. The roles of PKCs in regulating autophagy. J Cancer Res Clin Oncol 144, 2303–2311 (2018). https://doi.org/10.1007/s00432-018-2731-4

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Keywords

  • Autophagy
  • PKC-β
  • PKC-δ
  • PKC-α
  • Rottlerin