Related Experiment Video

Updated: Dec 7, 2025

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
08:01

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Published on: April 21, 2022

2.2K

Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy

Jiaming Xue1,2, Simone Patergnani3, Carlotta Giorgi3

  • 1Thoracic Oncology Program, University of Hawai'i Cancer Center, University of Hawai'i, Honolulu, HI 96813.

Proceedings of the National Academy of Sciences of the United States of America
|October 1, 2020
PubMed

Insights

High mobility group box 1 (HMGB1) protein released during asbestos exposure promotes autophagy, increasing human mesothelial cell survival and malignant transformation, a key mechanism in mesothelioma development.

Area of Science:

  • Cell Biology
  • Carcinogenesis
  • Biomarker Discovery

Background:

  • Asbestos exposure is a known cause of malignant transformation in human mesothelial cells (HM), leading to mesothelioma.
  • The precise mechanisms of asbestos-induced carcinogenesis are not fully understood, particularly how HM survive asbestos exposure to transform.
  • High mobility group box 1 (HMGB1) protein is released upon asbestos exposure and implicated in chronic inflammation and as a potential biomarker.

Purpose of the Study:

  • To elucidate the role of HMGB1 in asbestos-induced mesothelioma development.
  • To investigate the relationship between HMGB1, autophagy, and HM survival following asbestos exposure.
  • To identify HMGB1 as a potential therapeutic target for preventing asbestos-related cancers.

Main Methods:

  • Analysis of autophagy marker ATG5 in sera from asbestos-exposed individuals.
  • Investigation of HMGB1's effect on autophagy and HM survival in vitro.
  • Utilizing a novel mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model.
  • Assessment of autophagy inhibitors' impact on cell death and transformation.

Main Results:

  • HMGB1 release upon asbestos exposure promotes autophagy, enhancing HM survival and subsequent malignant transformation.
  • HMGB1 silencing or autophagy inhibition significantly increases asbestos-induced HM death and reduces transformation.
  • Cytoplasmic and extracellular HMGB1, via RAGE and Beclin 1 pathways, induce autophagy; nuclear HMGB1 is not involved.
  • HMGB1-cKO mice exhibit reduced autophagy and increased mesothelial cell death after asbestos exposure compared to wild-type.

Conclusions:

  • HMGB1-driven autophagy is a critical survival mechanism for human mesothelial cells exposed to asbestos.
  • This HMGB1-mediated autophagy promotes malignant transformation, contributing to mesothelioma pathogenesis.
  • Targeting HMGB1 or autophagy pathways presents a potential strategy for mesothelioma prevention and treatment.
Keywords:
HMGB1asbestosautophagycell deathmesothelioma

More Related Videos

Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice07:54

Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice

Published on: December 21, 2019

7.2K
Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model09:31

Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model

Published on: October 2, 2015

9.6K

Related Concept Videos

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...
5.0K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.5K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.1K
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
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.3K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.0K