Publications by authors named "Guohong Hu"

Oral tolerance is essential for intestinal homeostasis and systemic immune function. However, our understanding of how oral tolerance is maintained is inadequate. Here we report that food-derived nucleic acids promote oral tolerance through innate sensing pathways.

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  • Collective cell migration (CCM) is crucial for various biological processes like embryonic development, blood vessel formation, and tumor progression, but the specific mechanisms, especially regarding how leader cells are formed, are not well understood.
  • This study identifies a signaling pathway that regulates the cleavage of angiomotin (AMOT), showing that when AMOT is cleaved, it promotes leader cell formation and enhances the motility of cells within a group.
  • The cleavage of AMOT switches the cells from being tightly connected (which restricts movement) to a more fluid state that facilitates collective and coordinated migration, highlighting its role as a regulator in CCM.
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Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening.

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  • Recent research highlights the role of peptides and proteins from noncanonical open reading frames (ORFs) in disease, specifically identifying circTRIM1 in doxorubicin-resistant TNBC cells, linked to poor patient outcomes.
  • CircTRIM1 has a functional IRES and an 810 nt ORF that translates into a protein called TRIM1-269aa, which contributes to increased chemoresistance and metastasis in TNBC.
  • Mechanistically, TRIM1-269aa enhances the interaction between MARCKS and calmodulin, activating the PI3K/AKT/mTOR pathway, indicating circTRIM1/TRIM1-269aa could serve as a new target for TNBC therapy.
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Tumor heterogeneity, the presence of multiple distinct subpopulations of cancer cells between patients or among the same tumors, poses a major challenge to current targeted therapies. The way these different subpopulations interact among themselves and the stromal niche environment, and how such interactions affect cancer stem cell behavior has remained largely unknown. Here, it is shown that an FGF-BMP7-INHBA signaling positive feedback loop integrates interactions among different cell populations, including mammary gland stem cells, luminal epithelial and stromal fibroblast niche components not only in organ regeneration but also, with certain modifications, in cancer progression.

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. IL1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. In this study, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAM) to inhibit BTIC self-renewal and CD8+ T-cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models.

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Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy.

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ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1.

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The humidity of breath can serve as an important health indicator, providing crucial clinical information about human physiology. Significant progress had been made in the development of flexible humidity sensors. However, improving its humidity sensing performance (sensitivity and durability) is still facing many challenges.

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Patients with lung adenocarcinomas (LUAD) frequently develop metastasis. In this issue of Cancer Cell, Lengel et al. perform a comprehensive analysis of metastasis patterns in 2,532 LUAD samples to identify clinicopathologic and genomic features of LUAD tumors associated with metastatic development, burden, and organotropism.

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Estrogen receptor (ER)-positive luminal breast cancer is a subtype with generally lower risk of metastasis to most distant organs. However, bone recurrence occurs preferentially in luminal breast cancer. The mechanisms of this subtype-specific organotropism remain elusive.

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Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8 lymphocyte function, and enhanced tumor progression.

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Chronic inflammation and an immunosuppressive microenvironment promote prostate cancer (PCa) progression and diminish the response to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here, we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation-induced IKKβ activation to shape the immunosuppressive tumor microenvironment (TME).

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  • The study focuses on improving flexible pressure sensors using micro-engineered designs, specifically through a new method of incorporating microstructured arrays via aerosol printing as the intermediate dielectric layer (IDL).
  • This approach simplifies the production process and lowers costs while enhancing the sensor's sensitivity and response times, achieving notable performance metrics.
  • The sensors were tested in various applications (e.g., finger pressing and elbow bending) and demonstrated effective performance, suggesting that the aerosol printing method could replace traditional inverted mold techniques for sensor fabrication.
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Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype for its high rates of relapse, great metastatic potential, and short overall survival. How cancer cells acquire metastatic potency through the conversion of noncancer stem-like cells into cancer cells with stem-cell properties is poorly understood. Here, we identified the long noncoding RNA (lncRNA) TGFB2-AS1 as an important regulator of the reversibility and plasticity of noncancer stem cell populations in TNBC.

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Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts.

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Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis underlying the dissemination and outgrowth of tumor cells, why these cells can remain dormant for years, how they become resistant to the immune system or cytotoxic effects of systemic therapy, and how they interact with their new microenvironment. We asked experts to discuss some of the unknowns, advances, and areas of opportunity related to cancer metastasis.

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Estrogen receptor alpha (ER-α) action is critical for hormone-dependent breast cancer, and ER-α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)-resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER-α expression and the sensitivity of breast cancer cells to TAM.

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Three-dimensional microstructures play a key role in the fabrication of flexible electronic products. However, the development of flexible electronics is limited in further applications due to low positioning accuracy, the complex process, and low production efficiency. In this study, a novel method for fabricating three-dimensional circular truncated cone microstructures via low-frequency ultrasonic resonance printing is proposed.

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IFN-γ-stimulated MHC class I (MHC-I) antigen presentation underlies the core of antitumor immunity. However, sustained IFN-γ signaling also enhances the programmed death ligand 1 (PD-L1) checkpoint pathway to dampen antitumor immunity. It remains unclear how these opposing effects of IFN-γ are regulated.

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The protumor roles of alternatively activated (M2) tumor-associated macrophages (TAMs) have been well established, and macrophage reprogramming is an important therapeutic goal. However, the mechanisms of TAM polarization remain incompletely understood, and effective strategies for macrophage targeting are lacking. Here, we show that miR-182 in macrophages mediates tumor-induced M2 polarization and can be targeted for therapeutic macrophage reprogramming.

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Lipid droplets (LDs) have increasingly been recognized as an essential organelle for eukaryotes. Although the biochemistry of lipid synthesis and degradation is well characterized, the regulation of LD dynamics, including its formation, maintenance, and secretion, is poorly understood. Here, we report that mice lacking Occludin (Ocln) show defective lipid metabolism.

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Endocytosis of cell surface receptors is essential for cell migration and cancer metastasis. Rab5, a small GTPase of the Rab family, is a key regulator of endosome dynamics and thus cell migration. However, how its activity is regulated still remains to be addressed.

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Background: Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP.

Objective: To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs).

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Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate premetastatic niche and bone tropism are largely unknown. In this study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis.

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