Related Experiment Video

Updated: Dec 11, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

514

The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy

Jimin Yuan1,2, Xiaoduo Dong3, Jiajun Yap4

  • 1Department of Urology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China. yuan.jimin@szhospital.com.

Journal of Hematology & Oncology
|August 19, 2020
PubMed

Insights

Cancer cells hijack the MAPK pathway for growth and survival, but AMPK signaling can regulate this. Targeting both pathways offers a novel therapeutic strategy for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Signaling

Background:

  • The Ras/RAF/MEK/ERK (MAPK) signaling pathway is frequently hyperactivated in over 40% of human cancers, driving uncontrolled cell proliferation.
  • MAPK signaling promotes cancer by activating proliferative genes and inhibiting AMP-activated protein kinase (AMPK) signaling, a crucial regulator of cellular metabolism.
  • Emerging evidence indicates that AMPK signaling can reciprocally regulate MAPK signaling in cancer cells, influencing carcinogenesis and therapeutic responses.

Purpose of the Study:

  • To review the intricate interplay between MAPK and AMPK signaling in cancer biology.
  • To discuss the clinical implications of targeting MAPK and AMPK pathways in cancer treatment.
  • To explore the potential of combination therapies involving MAPK inhibitors and AMPK modulators.

Main Methods:

  • Literature review of current research on MAPK-AMPK signaling crosstalk in cancer.
  • Analysis of the role of this interplay in carcinogenesis and cancer therapy outcomes.
  • Discussion of therapeutic strategies targeting both pathways.

Main Results:

  • MAPK hyperactivation is a hallmark of many cancers, promoting growth and metabolic adaptation.
  • AMPK signaling acts as a negative regulator of MAPK activity through phosphorylation of key kinases.
  • The interaction between MAPK and AMPK influences cancer progression and response to MAPK-targeted therapies.

Conclusions:

  • The crosstalk between MAPK and AMPK signaling is a critical determinant in cancer development and progression.
  • Modulating both MAPK and AMPK pathways presents a promising avenue for novel cancer therapeutics.
  • Combinatorial therapies targeting both signaling axes hold potential for improved clinical outcomes in cancer treatment.
Keywords:
AMPK activatorsAMPK inhibitorsAMPK signalingAutophagyCellular metabolismInterplayRAF/MEK/ERK inhibitorsRas/RAF/MEK/ERK signalingTargeted therapyTumorigenesis

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.0K
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.2K

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.0K
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...
4.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.6K
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...
8.5K
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...
7.5K