Single-cell RNA sequencing reveals the MIF-ACKR3 receptor-ligand interaction between iCAFs and tumor cells in esophageal squamous cell carcinoma

Liang, Jialu; Lei, Kai; Liang, Ruihao; Huang, Jing; Tan, Binhua; Lin, Huayue; Wang, Minghui

doi:10.1016/j.cellsig.2024.111093

Cited by 2 publications

References 34 publications

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Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities

Farghli,

Chan,

Sherman

et al. 2024

Preprint

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Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC. However, a significant drawback of these efforts is that they were conducted on bulk tumor samples. Consequently, identities and roles of distinct cell types within the tumor milieu, and the patterns of intercellular communication, have yet to be explored. In this study we unveil cell-type specific gene signatures, transcription factor networks, and super-enhancers in FLC using a multi-omics strategy that leverages both single-nucleus ATAC-seq and single-nucleus RNA-seq. We also infer completely rewired cell-to-cell communication patterns in FLC including signaling mediated by SPP1-CD44, MIF-ACKR3, GDF15-TGFBR2, and FGF7-FGFR. Finally, we validate findings with loss-of-function studies in several models including patient tissue slices, identifying vulnerabilities that merit further investigation as candidate therapeutic targets in FLC.

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Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities

Farghli,

Chan,

Sherman

et al. 2024

Preprint

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A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy

Zhao,

Jia,

Sun

et al. 2024

Front. Immunol.

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IntroductionBladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits.MethodsResearchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment.ResultsA distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2’s role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration.DiscussionThe findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.

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Single-cell RNA sequencing reveals the MIF-ACKR3 receptor-ligand interaction between iCAFs and tumor cells in esophageal squamous cell carcinoma

Cited by 2 publications

References 34 publications

Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities

Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities

A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy

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