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MCT4 deficiency suppresses tumor incidence and metastasis by downregulating IGF1 expression and enhancing anti-tumor

Shuo Wang1, Hailing Guo1, Lujin Feng1

  • 1Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, China.

Communications Biology
|April 20, 2026
PubMed

Insights

Monocarboxylate transporter 4 (MCT4) drives cancer growth by regulating IGF1 and suppressing antitumor immunity. Knocking out MCT4 significantly reduces tumor volume and incidence, revealing its therapeutic potential.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Monocarboxylate transporter 4 (MCT4/SLC16A3) is upregulated in cancers, correlating with aggressive disease and poor outcomes.
  • Its precise functional role in tumorigenesis and immune evasion remains to be fully elucidated.

Purpose of the Study:

  • To investigate the functional role of MCT4 in cancer progression and antitumor immunity.
  • To determine the impact of MCT4 deficiency on tumor growth, IGF1 production, and immune cell infiltration.

Main Methods:

  • Generation of MCT4 homozygous knockout BALB/c mice (MCT4-/-) using CRISPR/Cas9-EGE technology.
  • Assessment of tumor volume, IGF1 levels (circulating and interstitial), and immune cell populations (CD4⁺/CD8⁺ T cells, NK cells, macrophages) in allograft models.
  • Evaluation of tumor incidence and lesion development in three independent carcinogenesis models (breast, lung, oral squamous).

Main Results:

  • MCT4-/- mice showed a ~40% reduction in allograft tumor volume compared to wild-type mice.
  • IGF1 levels were decreased by 40-45% in MCT4-/- mice, and exogenous IGF1 restored tumor growth.
  • MCT4 deficiency enhanced antitumor immunity, increasing T cell, NK cell, and macrophage infiltration, with a shift from M2 to M1 macrophages.
  • MCT4-/- mice developed fewer and smaller lesions across multiple cancer models.

Conclusions:

  • MCT4 is a key driver of carcinogenesis, influencing tumor growth via IGF1 regulation.
  • MCT4 deficiency enhances antitumor immunity by modulating immune cell infiltration and phenotype.
  • Targeting MCT4 represents a promising therapeutic strategy for cancer treatment.

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