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Predictive and prognostic markers
MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer

MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer

Hao Wang ¹, Kexin He ¹, Ruixue Huo ¹, Weihan Li ¹, Shan Zhang ², Lu-Ju Jiang ², Hao Wu ¹, Minhao Yu ³, Shu-Heng Jiang ², Junli Xue ¹

Hao Wang ¹, Kexin He ¹, Ruixue Huo ¹

¹Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China.
²State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
³Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China.

⁰Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, P. R. China.

Advanced Science (weinheim, Baden-Wurttemberg, Germany) +

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March 27, 2025

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March 27, 2025

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View abstract on PubMed

Summary

This summary is machine-generated.

MAGEA6 drives colorectal cancer (CRC) nerve invasion by recruiting Schwann cells. Inhibiting MAGEA6 may offer a new therapeutic strategy for treating advanced CRC and improving patient prognosis.

Area Of Science

Oncology
Molecular Biology
Cancer Research

Background

Perineural invasion (PNI) in colorectal cancer (CRC) is linked to poor patient outcomes.
Understanding the molecular mechanisms driving PNI is essential for developing novel therapeutic strategies.

Purpose Of The Study

To investigate the role of MAGEA6 in colorectal cancer perineural invasion.
To elucidate the molecular mechanisms by which MAGEA6 influences PNI and tumor progression.

Main Methods

Analysis of TCGA database for clinical and transcriptome data.
Generation of MAGEA6 knockdown CRC cell lines and assessment of invasion.
Utilized rectal orthotopic and sciatic nerve invasion models.
Investigated Schwann cell recruitment via ssGSEA and co-culture experiments.

Main Results

MAGEA6 expression correlates with poor prognosis in CRC patients.
MAGEA6 knockdown significantly reduces CRC cell migration, invasion, and PNI.
CRC cells recruit Schwann cells (SCs) through CXCL1, a process promoted by MAGEA6.
MAGEA6 stabilizes YY1, enhancing CXCL1 transcription and subsequent SC recruitment.

Conclusions

MAGEA6 is a key regulator of PNI in colorectal cancer.
MAGEA6 promotes CRC invasiveness and PNI by stabilizing YY1, leading to increased CXCL1 secretion and SC recruitment.
Targeting MAGEA6 represents a potential therapeutic avenue for managing PNI in CRC.

Keywords:

cancer neuroscience melanoma‐associated antigen a6 perineural invasion schwann cell yin‐yang 1

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Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

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