ArticleCell & bioscience2024
MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning.
Article in Cell & bioscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- Review
- MIIP Inhibits Colorectal Cancer Progression by Modulating Neutrophils Infiltration and Neutrophil Extracellular Trap Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Visceral and subcutaneous adipose stem cells modulate colorectal cancer cell progression: direct and indirect contact distinctly accelerate tumor aggressiveness.Molecular medicine (Cambridge, Mass.) · 2026Article
- MRI-based habitat, intra-, and peritumoral machine learning model for perineural invasion prediction in rectal cancer.Abdominal radiology (New York) · 2026Article
- Migration and invasion inhibitory protein inhibits M2 macrophage polarization to suppress colorectal cancer progression through the STING-NFκB2-IL10 axis.Cancer biology & medicine · 2026Article
- TRIM22 governs tumorigenesis and protects against endometrial cancer-associated cachexia by inhibiting inflammatory response and adipose thermogenic activity.Cancer & metabolism · 2025Article
- CKAP2 Regulated by TFDP1 Promotes Metastasis and Proliferation of Colorectal Cancer through Affecting the Tumor Microenvironment.Journal of microbiology and biotechnology · 2024Article
- The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC.
resultsMIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression.
conclusionsOur data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.