Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis DOI Creative Commons
Hong Sheng Quah, Elaine Yiqun Cao, Lisda Suteja

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 27, 2023

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation pre-metastatic cells, driven by actionable pathways including AXL AURK. Blocking these two proteins blunts tumor invasion patient-derived cultures. Furthermore, scRNAseq analyses tumor-infiltrating CD8 + T-lymphocytes show distinct T-cell dysfunction, corroborated their clonal architecture based on receptor sequencing. By determining key modulators trajectories, followed validation using external datasets functional experiments, we uncover role for SOX4 mediating exhaustion. Finally, interactome between cells putative the Midkine pathway immune-modulation this is confirmed from humanized mice. Aside specific findings, study demonstrates importance heterogeneity identifying vulnerabilities during early metastasis.

Language: Английский

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis DOI Open Access
Arpita Datta, Shuo Deng, Vennila Gopal

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(8), P. 1882 - 1882

Published: April 14, 2021

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal called to transition (EMT). The cytoskeleton an active network three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play central role in structural design cell behavior are necessary for EMT. During EMT, undergo as manifested by elongation, migration, invasion, coordinated reorganization. extremely dynamic structure, controlled balance assembly disassembly Actin-binding proteins regulate polymerization depolymerization. Microtubule reorganization also plays important migration polarization. Intermediate rearranged, switching vimentin-rich network, this protein used marker cell. Hence, targeting EMT regulating activities their key components may be potential solution metastasis. This review summarizes research done on physiological functions its process, effect multidrug-resistant (MDR) cells—highlight some future perspectives therapy cytoskeleton.

Language: Английский

Citations

122

Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures DOI Creative Commons
Bing Feng, Jian Wu, Bo Shen

et al.

Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)

Published: April 29, 2022

Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME) with diverse functions such as extracellular matrix (ECM) remodeling, modulation metabolism and angiogenesis, crosstalk both cancer cells infiltrating immune by production growth factors, cytokines, chemokines. Within TME milieu, CAFs exhibit morphological functional transitions relatively specific markers hold tremendous potential to facilitate tumorigenesis, development, resistance towards multiple therapeutic strategies including chemotherapy, radiotherapy, targeted therapy, anti-angiogenesis immunotherapy, endocrine therapy. Accordingly, themselves downstream effectors and/or signaling pathways targets for optimizing sensitivity anti-cancer therapies. This review aims provide a detailed landscape role that play in conferring different cancers underlying mechanisms. The translational perspectives individualized treatment malignant tumors also discussed.

Language: Английский

Citations

113

Heterogeneity and plasticity of epithelial–mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms DOI Creative Commons

Dandan Li,

Lingyun Xia,

Pan Huang

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(6)

Published: Feb. 19, 2023

Epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single-cell sequencing, have revealed that EMT is not a binary process, but heterogeneous and dynamic disposition with intermediary partial states. Multiple double-negative feedback loops involved by EMT-related transcription factors (EMT-TFs) been identified. These between drivers MET finely regulate the state of cell. In this review, general characteristics, biomarkers molecular mechanisms different states were summarized. We additionally discussed direct indirect tumour More importantly, article provides evidence heterogeneity closely related to poor prognosis gastric cancer. Notably, seesaw model was proposed explain how cells themselves remain specific states, including epithelial state, hybrid/intermediate mesenchymal state. Additionally, also review current status, limitations future perspectives signalling clinical applications.

Language: Английский

Citations

78

Anticancer potential of allicin: A review DOI
Elena Catanzaro, Donatella Canistro,

Valentina Pellicioni

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 177, P. 106118 - 106118

Published: Feb. 5, 2022

Language: Английский

Citations

77

Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis DOI Creative Commons
Hong Sheng Quah, Elaine Yiqun Cao, Lisda Suteja

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 27, 2023

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation pre-metastatic cells, driven by actionable pathways including AXL AURK. Blocking these two proteins blunts tumor invasion patient-derived cultures. Furthermore, scRNAseq analyses tumor-infiltrating CD8 + T-lymphocytes show distinct T-cell dysfunction, corroborated their clonal architecture based on receptor sequencing. By determining key modulators trajectories, followed validation using external datasets functional experiments, we uncover role for SOX4 mediating exhaustion. Finally, interactome between cells putative the Midkine pathway immune-modulation this is confirmed from humanized mice. Aside specific findings, study demonstrates importance heterogeneity identifying vulnerabilities during early metastasis.

Language: Английский

Citations

67