# Hsp70 regulates CD24 expression and promotes metastasis and invasion of lung cancer via the MAPK/ERK signaling pathway

**Authors:** Xin Liu, Xinjing Yu, Qun Hu, Ning Zhang, Shuyu Zhang, Yang Liu, Jiaqi Jia, Xiaojuan Qiao

PMC · DOI: 10.3389/fonc.2025.1665342 · Frontiers in Oncology · 2025-10-21

## TL;DR

This study shows that Hsp70 increases CD24 levels and promotes lung cancer spread through the MAPK/ERK pathway.

## Contribution

The novel finding is that Hsp70 regulates CD24 and enhances lung cancer metastasis via the MAPK/ERK signaling pathway.

## Key findings

- Hsp70 knockdown reduced CD24 expression and inhibited cancer cell invasion and metastasis.
- CD24 overexpression enhanced oncogenic properties like migration and angiogenesis.
- Hsp70 activates the MAPK/ERK pathway to promote lung cancer progression.

## Abstract

To investigate the effects and mechanisms of Hsp70-mediated regulation of CD24 expression on the invasion and metastasis of lung cancer.

Protein-protein interactions between Hsp70 and CD24 were analyzed by co-immunoprecipitation and immunofluorescence. Lentiviral-mediated Hsp70 knockdown and CD24 overexpression were validated using RT-qPCR and Western blotting. Functional consequences were assessed through CCK-8 proliferation assays, colony formation, wound healing, Transwell migration/invasion, and angiogenesis assays. In vivo metastatic potential was evaluated using a tail vein injection model in nude mice.

Hsp70 and CD24 demonstrated interaction through co-precipitation. Knockdown of Hsp70 significantly attenuated CD24 expression (p<0.01), whereas CD24 overexpression did not alter Hsp70 levels. Phenotypically, Hsp70 suppression impaired cellular proliferation, migration, invasion and angiogenic capacity, while CD24 overexpression potentiated these oncogenic properties. Both manipulations modulated ERK1/2, MEK, Raf and Ras phosphorylation status.

Hsp70 upregulates CD24 expression and activates downstream MAPK/ERK signaling, thereby enhancing the metastatic and invasive capacity of lung cancer.

## Linked entities

- **Genes:** HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 3303], CD24 (CD24 molecule) [NCBI Gene 100133941], erk1/2 (mitogen-activated protein kinase) [NCBI Gene 778596], MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609], ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882], ras (resistance to audiogenic seizures) [NCBI Gene 19412]
- **Proteins:** HSPA1A (heat shock protein family A (Hsp70) member 1A), CD24 (CD24 molecule), erk1/2 (mitogen-activated protein kinase), MAP2K7 (mitogen-activated protein kinase kinase 7), ZHX2 (zinc fingers and homeoboxes 2), ras (resistance to audiogenic seizures)
- **Diseases:** lung cancer (MONDO:0005138)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Hspa1b (heat shock protein family A (Hsp70) member 1B) [NCBI Gene 15511] {aka HSP70B1, Hsp70, Hsp70-1, Hsp70.1, hsp68}, Zhx2 (zinc fingers and homeoboxes 2) [NCBI Gene 387609] {aka Afr-1, Afr1, Raf, mKIAA0854}, Cd24a (CD24a antigen) [NCBI Gene 12484] {aka Cd24, HSA, Ly-52, nectadrin}, Mdk (midkine) [NCBI Gene 17242] {aka MK, Mek}
- **Diseases:** metastatic (MESH:D000092182), metastasis (MESH:D009362), lung cancer (MESH:D008175)
- **Chemicals:** CCK-8 (MESH:D012844)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12583058/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12583058/full.md

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Source: https://tomesphere.com/paper/PMC12583058