AMPK signaling and its targeting in cancer progression and treatment.

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Date

2022-10

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Abstract

The intrinsic mechanisms sensing the imbalance of energy in cells are pivotal for cell survival under various environmental insults. AMP-activated protein kinase (AMPK) serves as a central guardian maintaining energy homeostasis by orchestrating diverse cellular processes, such as lipogenesis, glycolysis, TCA cycle, cell cycle progression and mitochondrial dynamics. Given that AMPK plays an essential role in the maintenance of energy balance and metabolism, managing AMPK activation is considered as a promising strategy for the treatment of metabolic disorders such as type 2 diabetes and obesity. Since AMPK has been attributed to aberrant activation of metabolic pathways, mitochondrial dynamics and functions, and epigenetic regulation, which are hallmarks of cancer, targeting AMPK may open up a new avenue for cancer therapies. Although AMPK is previously thought to be involved in tumor suppression, several recent studies have unraveled its tumor promoting activity. The double-edged sword characteristics for AMPK as a tumor suppressor or an oncogene are determined by distinct cellular contexts. In this review, we will summarize recent progress in dissecting the upstream regulators and downstream effectors for AMPK, discuss the distinct roles of AMPK in cancer regulation and finally offer potential strategies with AMPK targeting in cancer therapy.

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Humans, Neoplasms, Signal Transduction, Epigenesis, Genetic, Energy Metabolism, AMP-Activated Protein Kinases

Citation

Published Version (Please cite this version)

10.1016/j.semcancer.2021.04.006

Publication Info

Hsu, Che-Chia, Danni Peng, Zhen Cai and Hui-Kuan Lin (2022). AMPK signaling and its targeting in cancer progression and treatment. Seminars in cancer biology, 85. pp. 52–68. 10.1016/j.semcancer.2021.04.006 Retrieved from https://hdl.handle.net/10161/33826.

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Scholars@Duke

Hsu

Che-Chia Hsu

Assistant Professor of Pathology

My research has focused on mitochondrial functions in cancer metabolism and understand the role of mitochondrial dynamics in cellular function and human diseases including cancers. Additionally, I also continuously dissect cancer metabolism and identifying potential metabolic vulnerabilities of cancer initiation, progression and metastasis using several in vitroex vivo and in vivo genetical approaches such as CRISPR/Cas9 knockout, mouse/ human organoid cultures and genetically engineered mouse models, thereby characterizing molecular mechanisms regulated by metabolic pathways and developing potential metabolic interventions for targeting cancers. 

Lin

Hui-Kuan Lin

Fred and Janet Sanfilippo Distinguished Professor

The research interest in Dr. Lin lab is to understand oncogenic networks between oncogenes and tumor suppressor genes, dissect the regulatory mechanisms underlying  the crosstalk between ageing and cancer, to unravel the role of posttranslational modifications (PTMs) such as ubiquitination  and metabolism in diverse molecular and biological processes important for cancer progression and metastasis, cancer stem regulation, cancer immunity and drug resistance by using biochemical and molecular approaches along with and genetic mouse models, and finally to develop small molecule inhibitors and antibodies targeting critical oncogenic signaling and metabolic vulnerabilities for cancer treatment. His research goals aim to not only reveal fundamental insights and concepts for cancer biology and cancer immunity, but also develop novel paradigms and therapeutic strategies for targeting human cancer and overcoming drug resistance.

Research interests include:

  • Crosstalk between oncogenic and tumor suppressor networks
  • Posttranslational modifications in signaling and cancer
  • Cancer progression and metastasis
  • Biology of normal and cancer stem cells
  • Metabolism in cancer and ageing

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