# Mitophagy and Bip–PERK–eIF2α–ATF4 Axis‐Mediated ER Stress Mediate Miriplatin‐Loaded Liposome's Anti‐Colorectal Cancer Action

**Authors:** Cong Zhao, Yuhan Qiu, Xiaowei Wang, Mengyan Wang, Li Liu, Xiaojun Zhao, Zixiang Gao, Rongguang Shao, Guimin Xia, Wuli Zhao

PMC · DOI: 10.1111/cpr.70153 · 2025-12-19

## TL;DR

A drug-loaded liposome fights breast cancer by triggering cell stress and death through specific pathways.

## Contribution

The study reveals a new mechanism of anti-cancer action involving mitophagy and ER stress pathways.

## Key findings

- Miriplatin-loaded liposomes induce mitophagy via lysosome-mitochondria fusion.
- ER stress is activated through the Bip–PERK–eIF2α–ATF4 axis, leading to apoptosis.
- The treatment shows anti-breast cancer effects via caveolin-mediated endocytosis.

## Abstract

LMPt enters the cell mainly through caveolin‐mediated endocytosis, and then fuses with endosomes and lysosomes to deliver MPt to mitochondria and the endoplasmic reticulum to induce mitophagy based on the fusion of lysosomes and mitochondria, and endoplasmic reticulum stress and subsequent apoptosis via the Bip–PERK–eIF2α–ATF4 axis to exert an anti‐breast cancer effect.

## Linked entities

- **Genes:** GDF10 (growth differentiation factor 10) [NCBI Gene 2662], EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 9451], EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939], ATF4 (activating transcription factor 4) [NCBI Gene 468]
- **Chemicals:** Miriplatin (PubChem CID 9832045)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 9451] {aka PEK, PERK, WRS}, EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939] {aka CDA02, EIF-2A, MST089, MSTP004, MSTP089}, ATF4 (activating transcription factor 4) [NCBI Gene 468] {aka CREB-2, CREB2, TAXREB67, TXREB}, HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309] {aka BIP, GRP78, HEL-S-89n}
- **Diseases:** breast cancer (MESH:D001943), Liposome (MESH:D015223), Colorectal Cancer (MESH:D015179)
- **Chemicals:** Miriplatin (MESH:C406530)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961539/full.md

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Source: https://tomesphere.com/paper/PMC12961539