Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling

Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mut...

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Published inNature communications Vol. 9; no. 1; pp. 5105 - 16
Main Authors Liu, Shu-Chen, Hsu, Tien, Chang, Yu-Sun, Chung, An-Ko, Jiang, Shih Sheng, OuYang, Chun-Nan, Yuh, Chiou-Hwa, Hsueh, Chuen, Liu, Ya-Ping, Tsang, Ngan-Ming
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.11.2018
Nature Publishing Group
Nature Portfolio
Subjects
13
13/106
13/21
13/51
13/95
14
14/1
631/67
692/4017
692/4028
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Adhesion
Adult
Aged
Aged, 80 and over
Animals
Blotting, Western
Cancer
Epithelial-Mesenchymal Transition - genetics
Epithelial-Mesenchymal Transition - physiology
Female
Focal adhesion kinase
Focal Adhesion Kinase 1 - genetics
Focal Adhesion Kinase 1 - metabolism
Human Umbilical Vein Endothelial Cells
Humanities and Social Sciences
Humans
Immunohistochemistry
Invasiveness
Kinases
Leukemia
Leukemia inhibitory factor
Leukemia Inhibitory Factor - genetics
Leukemia Inhibitory Factor - metabolism
Male
Mesenchyme
Metastases
Metastasis
Mice
Mice, SCID
Middle Aged
Migration
multidisciplinary
Nasopharyngeal carcinoma
Nasopharyngeal Carcinoma - genetics
Nasopharyngeal Carcinoma - metabolism
Nasopharyngeal Carcinoma - pathology
Nasopharyngeal Neoplasms - genetics
Nasopharyngeal Neoplasms - metabolism
Nasopharyngeal Neoplasms - pathology
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Neoplasm Metastasis
Paxillin - genetics
Paxillin - metabolism
Phosphoproteins - genetics
Phosphoproteins - metabolism
Receptors, OSM-LIF - genetics
Receptors, OSM-LIF - metabolism
Science
Science (multidisciplinary)
Signal Transduction - genetics
Signal Transduction - physiology
Signaling
Throat cancer
Transcription Factors
Xenograft Model Antitumor Assays
Yes-associated protein
Young Adult
Online AccessGet full text

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Abstract Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis. Molecular pathways regulating nasopharyngeal carcinoma (NPC) metastasis are unclear. Here they report higher levels of cytoplasmic leukemia inhibitory factor (cLIF) and LIF receptor (LIFR) to correlate with higher metastasis in NPC patients, and show cLIF to promote NPC metastasis and vascular dissemination via the YAP1-FAK/PXN axis.
AbstractList Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis.Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis.
Molecular pathways regulating nasopharyngeal carcinoma (NPC) metastasis are unclear. Here they report higher levels of cytoplasmic leukemia inhibitory factor (cLIF) and LIF receptor (LIFR) to correlate with higher metastasis in NPC patients, and show cLIF to promote NPC metastasis and vascular dissemination via the YAP1-FAK/PXN axis.
Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis. Molecular pathways regulating nasopharyngeal carcinoma (NPC) metastasis are unclear. Here they report higher levels of cytoplasmic leukemia inhibitory factor (cLIF) and LIF receptor (LIFR) to correlate with higher metastasis in NPC patients, and show cLIF to promote NPC metastasis and vascular dissemination via the YAP1-FAK/PXN axis.
Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis.
ArticleNumber 5105
Author Tsang, Ngan-Ming
Chang, Yu-Sun
Hsu, Tien
Hsueh, Chuen
OuYang, Chun-Nan
Liu, Shu-Chen
Yuh, Chiou-Hwa
Chung, An-Ko
Jiang, Shih Sheng
Liu, Ya-Ping
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/30504771$$D View this record in MEDLINE/PubMed
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Nature Publishing Group
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
– name: Nature Portfolio
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Snippet Metastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF)...
Molecular pathways regulating nasopharyngeal carcinoma (NPC) metastasis are unclear. Here they report higher levels of cytoplasmic leukemia inhibitory factor...
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StartPage 5105
SubjectTerms 13
13/106
13/21
13/51
13/95
14
14/1
631/67
692/4017
692/4028
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Adhesion
Adult
Aged
Aged, 80 and over
Animals
Blotting, Western
Cancer
Epithelial-Mesenchymal Transition - genetics
Epithelial-Mesenchymal Transition - physiology
Female
Focal adhesion kinase
Focal Adhesion Kinase 1 - genetics
Focal Adhesion Kinase 1 - metabolism
Human Umbilical Vein Endothelial Cells
Humanities and Social Sciences
Humans
Immunohistochemistry
Invasiveness
Kinases
Leukemia
Leukemia inhibitory factor
Leukemia Inhibitory Factor - genetics
Leukemia Inhibitory Factor - metabolism
Male
Mesenchyme
Metastases
Metastasis
Mice
Mice, SCID
Middle Aged
Migration
multidisciplinary
Nasopharyngeal carcinoma
Nasopharyngeal Carcinoma - genetics
Nasopharyngeal Carcinoma - metabolism
Nasopharyngeal Carcinoma - pathology
Nasopharyngeal Neoplasms - genetics
Nasopharyngeal Neoplasms - metabolism
Nasopharyngeal Neoplasms - pathology
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Neoplasm Metastasis
Paxillin - genetics
Paxillin - metabolism
Phosphoproteins - genetics
Phosphoproteins - metabolism
Receptors, OSM-LIF - genetics
Receptors, OSM-LIF - metabolism
Science
Science (multidisciplinary)
Signal Transduction - genetics
Signal Transduction - physiology
Signaling
Throat cancer
Transcription Factors
Xenograft Model Antitumor Assays
Yes-associated protein
Young Adult
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Title Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling
URI https://link.springer.com/article/10.1038/s41467-018-07660-6
https://www.ncbi.nlm.nih.gov/pubmed/30504771
https://www.proquest.com/docview/2139581492
https://www.proquest.com/docview/2149017418
https://pubmed.ncbi.nlm.nih.gov/PMC6269507
https://doaj.org/article/5859dcee62b843f5bc95e474b541df8d
Volume 9
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