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A 3D Organotypic Melanoma Spheroid Skin Model
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Endoplasmic reticulum stress in melanoma pathogenesis and resistance

Yi Kong1, Jian Jiang1, Yuqiong Huang1

  • 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan, Hubei Province 430022, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|October 22, 2022
PubMed

Insights

Melanoma cells face endoplasmic reticulum (ER) stress, activating the unfolded protein response (UPR). Targeting ER stress and UPR pathways offers new therapeutic strategies for melanoma treatment and overcoming drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Melanoma is an aggressive skin cancer with increasing incidence and limited treatment efficacy.
  • Drug resistance and poor prognosis remain significant clinical challenges in melanoma management.
  • Melanoma's genetic mutations and metabolic state induce endoplasmic reticulum (ER) stress, disrupting cellular protein balance (proteostasis).

Purpose of the Study:

  • To review the role of ER stress and the unfolded protein response (UPR) in melanoma.
  • To explore the interplay between ER stress, UPR, and melanoma pathogenesis and resistance.
  • To discuss therapeutic strategies targeting ER stress and UPR in melanoma.

Main Methods:

  • Literature review of studies on ER stress and UPR in melanoma.
  • Analysis of signaling pathways involved in ER stress and UPR.
  • Examination of the crosstalk between ER stress, UPR, and immune cells in the tumor microenvironment.

Main Results:

  • ER stress activates three UPR branches (IRE1α, PERK, ATF6), influencing melanoma cell fate.
  • ER stress and UPR are implicated in melanoma development and resistance to therapies.
  • Crosstalk exists between ER stress/UPR in melanoma cells and tumor-infiltrating immune cells.

Conclusions:

  • Understanding ER stress and UPR mechanisms is crucial for deciphering melanoma biology.
  • Targeting ER stress and UPR pathways presents a promising therapeutic avenue for melanoma.
  • Further research into ER stress and UPR modulation could improve melanoma patient outcomes.
Keywords:
ATF6ER stressIRE1MelanomaPERKUPR

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