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Updated: Jun 12, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

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EGF/EGFR-YAP1/TEAD2 signaling upregulates STIM1 in vemurafenib resistant melanoma cells

Weiyu Bai1, Chenghao Yan1, Yichen Yang2

  • 1Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China.

The FEBS Journal
|September 19, 2024
PubMed

Insights

Vemurafenib resistance increases Stromal Interaction Molecule 1 (STIM1) in melanoma by activating the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR)-Yes-associated protein 1 (YAP1)-TEA domain transcription factor 2 (TEAD2) pathway. This reveals a new therapeutic target for BRAF inhibitor resistance.

Area of Science:

  • Molecular Oncology
  • Cancer Cell Signaling
  • Melanoma Therapeutics

Background:

  • Stromal interaction molecule 1 (STIM1) is a key endoplasmic reticulum Ca2+ sensor implicated in cancer progression.
  • STIM1 is upregulated in vemurafenib-resistant melanoma, but the underlying mechanism remains unclear.
  • Vemurafenib is a serine/threonine-protein kinase B-raf inhibitor used in melanoma treatment.

Purpose of the Study:

  • To elucidate the mechanism by which vemurafenib resistance leads to STIM1 upregulation in melanoma.
  • To identify potential therapeutic strategies to overcome vemurafenib resistance in melanoma patients.

Main Methods:

  • Investigated the role of the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling pathway.
  • Assessed the involvement of Yes-associated protein 1 (YAP1) and TEA domain transcription factor 2 (TEAD2) in STIM1 regulation.
  • Utilized cell culture models of vemurafenib-resistant melanoma.

Main Results:

  • Vemurafenib resistance increases EGF and EGFR levels, activating the EGFR signaling pathway.
  • Activated EGFR signaling promotes YAP1 nuclear localization, enhancing STIM1 expression.
  • The identified pathway is EGF/EGFR-YAP1/TEAD2-STIM1.

Conclusions:

  • Vemurafenib resistance upregulates STIM1 via the EGF/EGFR-YAP1/TEAD2 signaling axis.
  • Targeting this axis offers a potential strategy to improve BRAF inhibitor efficacy in melanoma.
Keywords:
BRAF inhibitionEGF/EGFRSTIM1YAP1melanoma

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