Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies. Here, we identified a link between SHCBP1 and cilia in ductal carcinomas. Shcbp1 knockout in transgenic mice profoundly impeded tumor progression and metastasis, prolonging survival. Single-cell transcriptome analysis revealed a functional connection between SHCBP1 deficiency and increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR. Inhibition of tumor progression by SHCBP1 loss relied on the recovery of ciliogenesis. Analysis of a large cohort of patients with ductal carcinoma revealed a negative correlation between SHCBP1-induced ciliary loss and patient prognosis. Restoring ciliogenesis via SHCBP1 ablation elicited therapeutic effects in patient-derived xenograft models. Together, this study delineates that induction of MBR-centrosome proximity through SHCBP1-deficiency reactivates ciliogenesis, offering unique opportunities for the treatment of unciliated ductal carcinomas.

Ciliogenesis

Tumor progression

10.1158/0008-5472.can-24-1095

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Supplementary Data from PICH Activates Cyclin A1 Transcription to Drive S-Phase Progression and Chemoresistance in Gastric Cancer

Huili Ye Wengui Shi Jing Yang Long Wang Xiangyan Jiang

Supplementary figures and tables.

Transcription

Cyclin E

10.1158/0008-5472.24564615

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Redox-responsive metal-organic framework nanocapsules enhance tumor chemo-immunotherapy by modulating tumor metabolic reprogramming

Materials Today Bio (2025)

Yuman Dong Jieru Li Yiwei Dai Xinyu Zhang Tao Wang

Nanocapsules

Reprogramming

10.1016/j.mtbio.2025.101487

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Therapeutic strategies targeting uPAR potentiate anti–PD-1 efficacy in diffuse-type gastric cancer

Science Advances (2022)

Long Qin Long Wang Junchang Zhang Huinian Zhou Zhiliang Yang

The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer (GC) associated with low HER2 positivity rate and insensitivity to chemotherapy and immune checkpoint inhibitors. Here, we identify urokinase-type plasminogen activator receptor (uPAR) as a potential therapeutic target for DGC. We have developed a novel anti-uPAR monoclonal antibody, which targets the domains II and III of uPAR and blocks the binding of urokinase-type plasminogen activator to uPAR. We show that the combination of anti-uPAR and anti-Programmed cell death protein 1 (PD-1) remarkably inhibits tumor growth and prolongs survival via multiple mechanisms, using cell line-derived xenograft and patient-derived xenograft mouse models. Furthermore, uPAR chimeric antigen receptor-expressing T cells based on the novel anti-uPAR effectively kill DGC patient-derived organoids and exhibit impressive survival benefit in the established mouse models, especially when combined with PD-1 blockade therapy. Our study provides a new possibility of DGC treatment by targeting uPAR in a unique manner.

10.1126/sciadv.abn3774

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Exploring the role of PMEPA1 in gastric cancer

Molecular and Cellular Probes (2023)

Fei Wen Shangyu Yang Wei‐Wen Cai Mengyuan Zhao Long Qin

Although there are several treatments available for gastric cancer (GC), the prognosis of the disease is still poor due to many factors, such as late diagnosis and tumor heterogeneity. To identify potential therapeutic targets, bioinformatics techniques and clinical sample validation were employed and prostate transmembrane protein androgen induced 1 (PMEPA1) was selected for further study. In the present study, we found that elevated PMEPA1 expression correlates with a worse prognosis and weaker anti-tumor immunity in GC patients. Moreover, our study showed that PMEPA1 not only influences cell proliferation, clone formation, invasion, and migration in vitro, but also plays an important role in GC progression in vivo. Mechanically, PMEPA1 exerts its oncogenic effects through activating the Wnt/β-catenin signaling pathway. Therefore, PMEPA1 is a potential target for treating GC effectively.

clone (Java method)

10.1016/j.mcp.2023.101931

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Exploring the role of FBXO5 in gastric cancer

Molecular and Cellular Probes (2023)

Junchang Zhang Gengyuan Zhang Keshen Wang Feng Cui Hanteng Yang

Gastric cancer is one of the most common lethal malignancies in the world, especially in China. Due to the ineffective screening of early gastric cancer and drug resistance of the advanced, the prognosis of gastric cancer remains dismal. Based on bioinformatics and tissue microarray analyses, FBXO5 was selected for analysis in this study. Here, we report the function of FBXO5 in gastric cancer, showing for the first time that it contributes to tumor cell proliferation, clone formation, invasion and migration. In these preliminary findings, FBXO5 promoted the transition of the cell cycle from the G0/G1 to the G2/M phase, which likely resulted from FBXO5 interacting with CDK1 and NCAPG proteins. The relevant mechanism needs to be explored. In addition, FBXO5 participated in the tumor microenvironment and was negatively related to immune activation. FBXO5, an oncogene, plays a role in tumor initiation and progression, and is expected to be a potential target for gastric cancer treatment.

clone (Java method)

10.1016/j.mcp.2023.101915

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Targeting UBE2T suppresses breast cancer stemness through CBX6-mediated transcriptional repression of SOX2 and NANOG

Cancer Letters (2024)

Keshen Wang Qichen He Xiangyan Jiang Tao Wang Zhigang Li

Homeobox protein NANOG

10.1016/j.canlet.2024.217409

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Data from Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma

Wengui Shi Lianshun Li Huiming Zhao Zhengyang Li Zhijian Ma

<div>AbstractPrimary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies. Here, we identified a link between Shc1-binding protein (SHCBP1) and cilia in ductal carcinomas. Shcbp1 knockout in transgenic mice profoundly impeded tumor progression and metastasis, prolonging survival. Single-cell transcriptome analysis revealed a functional connection between SHCBP1 deficiency and increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR. Inhibition of tumor progression by SHCBP1 loss relied on the recovery of ciliogenesis. Analysis of a large cohort of patients with ductal carcinoma revealed a negative correlation between SHCBP1-induced ciliary loss and patient prognosis. Restoring ciliogenesis via SHCBP1 ablation elicited therapeutic effects in patient-derived xenograft models. Together, this study delineates that induction of MBR-centrosome proximity through SHCBP1-deficiency reactivates ciliogenesis, offering unique opportunities for the treatment of unciliated ductal carcinomas.Significance: SHCBP1 depletion rescues tumor ciliogenesis by enhancing Rab8 GTPase activity to restore the proximity of the midbody remnant to the centrosome, which impedes progression of ductal carcinomas and suggests potential therapeutic strategies.</div>

Ciliogenesis

Small GTPase

10.1158/0008-5472.c.7585342

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