Related Experiment Video

Updated: Oct 31, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.2K

Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes

Maria Apostolidi1,2, Ioannis A Vathiotis3, Viswanathan Muthusamy4,5

  • 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut.

Cancer Research
|June 29, 2021
PubMed

Insights

Targeting pyruvate kinase M2 (PKM2) phosphorylation at S37 shows promise for treating aggressive triple-negative breast cancer (TNBC). This study identifies PKM2pS37 as a biomarker and therapeutic target for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective biomarkers and targeted therapies.
  • Pyruvate kinase M2 (PKM2) is a key metabolic enzyme implicated in cancer development.
  • PKM2 phosphorylation, specifically at serine 37 (PKM2pS37), is linked to aggressive breast cancer phenotypes.

Purpose of the Study:

  • To investigate PKM2pS37 as a potential biomarker and therapeutic target in TNBC.
  • To explore the role of the cyclin-dependent kinase (CDK) pathway in PKM2 phosphorylation in TNBC.
  • To evaluate the efficacy of targeting the PKM2 regulatory axis in preclinical TNBC models.

Main Methods:

  • Identification and characterization of PKM2pS37 in TNBC patient samples.
  • Analysis of the association between PKM2pS37 and the CDK pathway in TNBC cells.
  • In vivo studies using a TNBC mouse xenograft model treated with PKM2 activator TEPP-46 and CDK inhibitor dinaciclib.

Main Results:

  • PKM2pS37 was identified as a prominent phosphoprotein with prognostic value in TNBC, exhibiting nuclear localization.
  • TEPP-46 reduced PKM2 nuclear localization, while both TEPP-46 and dinaciclib diminished PKM2pS37 levels and reduced tumor growth in vivo.
  • Combination therapy impaired cancer cell invasion, redox balance, and induced cell death.

Conclusions:

  • PKM2pS37 serves as a marker for aggressive TNBC phenotypes.
  • Targeting the PKM2 regulatory axis, particularly PKM2pS37, represents a promising therapeutic strategy for TNBC.
  • Combined inhibition of CDK and PKM2 activation may offer enhanced efficacy in treating TNBC.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.5K
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

11.6K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.5K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.2K