Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

PKM2 Knockdown Induces Autophagic Cell Death via the AKT/mTOR Pathway in Human Prostate Cancer Cells

Prasanta Dey
,
Amit Kundu
,
Richa Sachan
ORCID logo ,
Jaehyun Park
,
Mee Young Ahn
,
Kyungsil Yoon
,
Jaewon Lee
,
Nam Deuk Kim
ORCID logo ,
In Su Kim
,
Byung Mu Lee
,
Hyung Sik Kim
* ORCID logo
Version 1 : Received: 1 January 2019 / Approved: 3 January 2019 / Online: 3 January 2019 (12:32:52 CET)

How to cite: Dey, P.; Kundu, A.; Sachan, R.; Park, J.; Ahn, M.Y.; Yoon, K.; Lee, J.; Kim, N.D.; Kim, I.S.; Lee, B.M.; Kim, H.S. PKM2 Knockdown Induces Autophagic Cell Death via the AKT/mTOR Pathway in Human Prostate Cancer Cells. Preprints 2019, 2019010018. https://doi.org/10.20944/preprints201901.0018.v1 Dey, P.; Kundu, A.; Sachan, R.; Park, J.; Ahn, M.Y.; Yoon, K.; Lee, J.; Kim, N.D.; Kim, I.S.; Lee, B.M.; Kim, H.S. PKM2 Knockdown Induces Autophagic Cell Death via the AKT/mTOR Pathway in Human Prostate Cancer Cells. Preprints 2019, 2019010018. https://doi.org/10.20944/preprints201901.0018.v1

Abstract

Pyruvate kinase M2 (PKM2) is essential for aerobic glycolysis and is highly expressed in various cancer tissues. Although high PKM2 expression is observed in prostate cancer tissues, its functional role in cancer metabolism is unclear. Here, we investigated the role of PKM2 in regulating autophagy and its associated pathways in prostate cancer cells. PKM2 expression was silenced using various PKM2 small interfering RNAs (siRNAs) and then we measured PKM2-related cellular pathways associated with autophagy. PKM2 siRNA-transfected prostate cancer cells showed significantly reduced viability. Acridine orange staining and immunoblotting analysis showed that PKM2 downregulation markedly increased autophagic cell death. Results of western blotting analysis showed that PKM2 knockdown affected protein kinase B/mechanistic target of rapamycin 1 pathway, which consequently downregulated the expression of glycolytic enzymes lactate dehydrogenase A and glucose transporter 1. To the best of our knowledge, this is the first study to show that PKM2 inhibition alters cancer cell metabolism and induces autophagy. Thus, the present study provides a strategy for the development of PKM2-targeted novel anticancer drugs for the treatment of prostate cancer.

Keywords

pyruvate kinase M2; prostate cancer; cancer metabolism; mTOR; autophagy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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