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Poster Display session

186P - CIP2A modulates PKM2 dimer-tetramer transition through phosphorylation of serine 287 in non-small cell lung cancer


03 Apr 2022


Poster Display session


Pathology/Molecular Biology

Tumour Site

Non-Small Cell Lung Cancer


lijun Liang


Annals of Oncology (2022) 33 (suppl_2): S111-S116. 10.1016/annonc/annonc866


L. Liang1, Y. Zhang2, D. Wang3, F. Yang3, G. Zhou3

Author affiliations

  • 1 National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Balanced/CN
  • 2 Anhui Medical University, Hefei/CN
  • 3 National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing/CN

Abstract 186P


Pyruvate kinase M2 (PKM2), the final rate-limiting enzyme in glycolysis, exists in a dynamic population of monomer, dimer and tetramer that determine its pyruvate kinase activity. However, the roles of oncoproteins, such as the cancerous inhibitor of protein phosphatase PP2A (CIP2A) that is overexpressed in most human malignancies, in PKM2 dimer-tetramer switching remain largely unknown.


The CIP2A interacting proteins were analyzed by mass spectrometry sequencing and verified in cancer cells. The effects of CIP2A on PKM2 dimer-tetramer switching and cell metabolism were evaluated by size-exclusion chromatography and seahorse metabolic assays. The expression of CIP2A and phosphorylated PKM2 S287 in non-small cell lung cancer (NSCLC) was detected by immunohistochemistry assay, and the therapeutic efficacy of agents targeting CIP2A and PKM2 was tested in NSCLC murine model.


We reported that CIP2A could directly interact with PKM2 in NSCLC cells. CIP2A induced formation of PKM2 tetramer by phosphorylation of PKM2 at Ser287, which was shown to be critical for maintaining the tetramer state and activity of PKM2. In contrast, depletion of CIP2A promoted PKM2 dimer accumulation and translocation into the nucleus, resulting in the enhancement of glycolysis. Pharmacological inhibition of glycolysis or activation of PKM2 synergistically inhibited NSCLC cell growth when combined with CIP2A-targeting natural compound celastrol both in vitro and in vivo.


These results demonstrated that CIP2A determines PKM2 tetramer-dimer transition and controls the metabolic reprogramming of NSCLC cells.

Legal entity responsible for the study

The authors.


This work was supported by the National Key Research and Development Program of China (No. 2020YFA0803300), the Key Project of the National Natural Science Foundation of China (81830093), the CAMS Innovation Fund for Medical Sciences (CIFMS; Nos. 2021-RC310-003, 2020-RC310-002), CAMS Initiative for Innovative Medicine (2021-1-I2M-012), and the National Natural Science Foundation of China8 (2073092 and 81802796).


All authors have declared no conflicts of interest.

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