MUC1-mediated Macrophage Activation Promotes Colitis-associated Colorectal Cancer via Activating the Interleukin-6/ Signal Transducer and Activator of Transcription 3 Axis

Sheng, Yonghua; Davies, Joan E.; Wang, Ran; Wong, Kuan Yau; Giri, Rabina; Yang, Yuanhao; Begun, Jakob; Florin, Timothy H.; Hasnain, Sumaira Z.; McGuckin, Michael A.

doi:10.1016/j.jcmgh.2022.06.010

Cited by 8 publications

(4 citation statements)

References 69 publications

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“…The mucus layer on the surface of the intestinal cavity (and secreted mucins) protects the intestinal mucosa and resists bacterial invasion [ 88 ]. MUC1 is a cell-surface mucin of intestinal epithelial cells that protects epithelial cells and participates in signal transduction [ 89 , 90 ]. Our results show that colonic mucus secretion and MUC1 expression significantly decreased in the 8 μm and 70 μm PP-MP treatment groups at exposure concentrations of 1 mg/mL and 10 mg/mL.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice

Jia

Han²,

Liu³

et al. 2023

Toxics

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Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 μm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 μm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals.

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Section: Discussionmentioning

confidence: 99%

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice

Jia

Han²,

Liu³

et al. 2023

Toxics

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“…It has been demonstrated that MUC1 overexpression in epithelial tumor cells is essential to the transformation process, but little is known about MUC1′s function in immune cells throughout the development of cancer and in regulating the interaction between tumor cells and the immune system. Sheng et al demonstrated that in the azoxymethane (AOM)/dextran sulfate sodium (DSS) animal model of colitis-associated cancer (CAC), MUC1 acts as a neoplastic factor that controls macrophage infiltration and function and promotes a tumor-permissive environment that affects tumor initiation and progression to invasive cancer [ 85 ]. MUC1 has a significant role in immune cell signaling, which encourages the development of cancer linked to chronic inflammation.…”

Section: Muc1 In Human Carcinomamentioning

confidence: 99%

The Role of MUC1 in Renal Cell Carcinoma

Milella,

Rutigliano,

Lasorsa

et al. 2024

Biomolecules

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Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.

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“…In colitis-associated colorectal cancer (CAC), Sheng et al. found that abnormal overexpression of MUC1 significantly exacerbates tumor progression, while inhibiting MUC1 expression can reduce inflammation and tumor progression, marked by increased CD8+ T lymphocytes and reduced macrophages in tumors ( 109 ). Monti et al.…”

Section: The Role Of Muc1 and Muc16 In The Tumor Immune Microenvironmentmentioning

confidence: 99%

MUC1 and MUC16: critical for immune modulation in cancer therapeutics

Chen,

Sandrine,

Yang

et al. 2024

Front. Immunol.

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The Mucin (MUC) family, a range of highly glycosylated macromolecules, is ubiquitously expressed in mammalian epithelial cells. Such molecules are pivotal in establishing protective mucosal barriers, serving as defenses against pathogenic assaults. Intriguingly, the aberrant expression of specific MUC proteins, notably Mucin 1 (MUC1) and Mucin 16 (MUC16), within tumor cells, is intimately associated with oncogenesis, proliferation, and metastasis. This association involves various mechanisms, including cellular proliferation, viability, apoptosis resistance, chemotherapeutic resilience, metabolic shifts, and immune surveillance evasion. Due to their distinctive biological roles and structural features in oncology, MUC proteins have attracted considerable attention as prospective targets and biomarkers in cancer therapy. The current review offers an exhaustive exploration of the roles of MUC1 and MUC16 in the context of cancer biomarkers, elucidating their critical contributions to the mechanisms of cellular signal transduction, regulation of immune responses, and the modulation of the tumor microenvironment. Additionally, the article evaluates the latest advances in therapeutic strategies targeting these mucins, focusing on innovations in immunotherapies and targeted drugs, aiming to enhance customization and accuracy in cancer treatments.

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MUC1-mediated Macrophage Activation Promotes Colitis-associated Colorectal Cancer via Activating the Interleukin-6/ Signal Transducer and Activator of Transcription 3 Axis

Cited by 8 publications

References 69 publications

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice

The Role of MUC1 in Renal Cell Carcinoma

MUC1 and MUC16: critical for immune modulation in cancer therapeutics

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