Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

6.4K
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...
6.4K
Abnormal Proliferation02:23

Abnormal Proliferation

4.7K
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...
4.7K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

7.0K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.0K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

6.7K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Iron-catalyzed oxidative stress reveals an exposome-related ferroptosis-resistant karyomegalic niche in BRCA1-linked renal carcinogenesis.

Redox biology·2026
Same author

Compressive stress inhibits proliferation in AsPC-1 pancreatic cancer cells and reduction of Myc protein.

PloS one·2026
Same author

Possible involvement of the mesenchymal cell marker Meflin in regeneration after retinal injury.

Scientific reports·2026
Same author

CCL5 enhances invasion of squamous cell carcinoma via syndecan-1-dependent ERK signaling.

Cell structure and function·2026
Same author

Meflin confers antifibrotic properties to intestinal fibroblasts in inflammatory bowel disease.

The Journal of clinical investigation·2026
Same author

Differential roles of ATM and Chk2 in cold atmospheric helium plasma-induced cell death in Molt-4 human leukemia cell with intact or reduced p53 expression.

Biochemical and biophysical research communications·2026

Related Experiment Video

Updated: Oct 6, 2025

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
08:22

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model

Published on: October 27, 2020

3.1K

Decrease in MAP3Ks expression enhances the cell death caused by hyperthermia.

Atsushi Enomoto1, Takemichi Fukasawa1,2, Hiroshi Terunuma3

  • 1Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
|January 19, 2022
PubMed
Summary

Hyperthermia triggers cancer cell death by reducing key proteins TAK1, RAF1, and MEKK2. These MAP3K proteins are crucial for cell proliferation and clonogenicity, making them potential targets for anticancer therapies.

Keywords:
HyperthermiaMAP3Kcalciumcalpainclonogenicity

More Related Videos

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
04:20

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

1.1K
Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform
11:08

Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform

Published on: January 13, 2019

12.5K

Related Experiment Videos

Last Updated: Oct 6, 2025

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
08:22

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model

Published on: October 27, 2020

3.1K
Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
04:20

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

1.1K
Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform
11:08

Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform

Published on: January 13, 2019

12.5K

Area of Science:

  • Biochemistry
  • Molecular Oncology
  • Cell Biology

Background:

  • Hyperthermia is a recognized anticancer treatment.
  • The precise molecular mechanisms behind thermal sensitivity in tumor cells remain unclear.
  • Understanding these mechanisms is vital for optimizing hyperthermia as a therapeutic strategy.

Purpose of the Study:

  • To elucidate the biochemical alterations induced by heat that contribute to antitumor activity.
  • To investigate the role of Mitogen-Activated Protein Kinase (MAPK) pathway components in hyperthermia-induced cell death.
  • To identify specific molecular targets within the MAPK pathway affected by hyperthermia.

Main Methods:

  • Western blotting and RT-PCR were used to assess MAPK member expression in HeLa cells.
  • Intracellular calcium levels ([Ca2+]i) were monitored using digital imaging.
  • Calpain activity and its role in MAPK component cleavage were examined via in vitro assays.
  • Cell proliferation and clonogenicity were evaluated using siRNA knockdown of specific MAPK members.

Main Results:

  • Hyperthermia decreased levels of MAP3K members TAK1, RAF1, and MEKK2, but not downstream MAP2K or MAPK components.
  • Heat-induced degradation of TAK1 and MEKK2 was mediated by calpain and proteasome pathways.
  • RAF1 downregulation was observed, independent of proteasome or calpain inhibition.
  • Increased intracellular calcium and calpain I expression correlated with hyperthermia.
  • Knockdown of TAK1, RAF1, or MEKK2 significantly suppressed cell proliferation and clonogenicity.

Conclusions:

  • Hyperthermia reduces specific MAP3K proteins (TAK1, RAF1, MEKK2) via calpain-dependent degradation or transcriptional changes.
  • These MAP3K proteins are critical for tumor cell proliferation and clonogenicity.
  • TAK1, RAF1, and MEKK2 represent potential molecular targets for enhancing hyperthermia-based cancer treatments.