<scp>CK</scp>1ε and p120‐catenin control Ror2 function in noncanonical Wnt signaling

Curto, Josué; Valle-Pérez, Beatriz Del; Villarroel, Aida; Fuertes, Guillem; Vinyoles, Meritxell; Peña, Raúl; Herreros, Antonio Garcı́a de; Duñach, Mireia

doi:10.1002/1878-0261.12184

Cited by 15 publications

(12 citation statements)

References 59 publications

(86 reference statements)

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“…Among the four downregulated genes found to be differentially expressed between the two extreme discovery cohorts, three were cancer‐related genes (i.e., ROR2 , CLDN15 and GLTPD1 ) and one was not previously related to cancer (i.e., TMEM150B ). ROR2 belongs to the superfamily of transmembrane glycoproteins that are involved in the control of several basic cellular processes including cell proliferation, differentiation, migration and metabolism . GLTPD1 , ceramide‐1‐phosphate transfer protein, has been shown to induce prostaglandin signaling and inflammation in A549 human lung cancer cells .…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Mini

Lapucci

Perrone

et al. 2019

Intl Journal of Cancer

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Five‐year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs. favorable prognosis) were selected. RNA‐sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to disease‐free survival (DFS), 108 differentially expressed genes (104/4 up/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancer‐related genes (n = 14) and cancer‐unrelated genes (n = 16). Three out of four down‐regulated genes were cancer‐related. Mutational status (i.e., RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p = 0.018 and p = 0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT.

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Section: Discussionmentioning

confidence: 99%

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Mini

Lapucci

Perrone

et al. 2019

Intl Journal of Cancer

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“…In our OA chondrocyte model, we observed phosphorylation of Dvl and p120 catenin. According to previous studies, p120 catenin assists CK1ε to control Ror2 function, leading to JNK activation . Therefore, the role of p120 catenin in CK1ε‐mediated OA is worthy of further investigation.…”

Section: Discussionmentioning

confidence: 90%

“…After IL‐1β treatment for 8 hours, western blot showed a clear phosphorylation shift of Dishevelled (Dvl; Figure 3C), which is widely considered a substrate of CK1ε . P120 catenin was reported to be phosphorylated at Ser268 by CK1ε as well . After stimulation with IL‐1β, phosphorylated p120 catenin was also upregulated in a dose‐dependent manner (Figure 3D), which could be inhibited by PF4800567 (Figure 3E).…”

Section: Resultsmentioning

confidence: 96%

“…However, since CK1ε was not directly targeted in this study, its role in OA cannot be inferred simply based on its participation in Wnt pathway signaling. Distinct from other variants, CK1ε also plays a role in circadian rhythm and c‐Jun N‐terminal kinase (JNK) signaling, whose dysregulation is considered to contribute to OA, implicating a high correlation between CK1ε and OA. However, a direct connection between OA and CK1ε has never been reported.…”

Section: Introductionmentioning

confidence: 99%

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Casein kinase 1 epsilon facilitates cartilage destruction in osteoarthritis through JNK pathway

et al. 2020

FASEB j.

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Tianwei He, Depeng Wu and Lei He are contributed equally to the manuscript.Abbreviations: CK1ε, casein kinase 1 epsilon; IL-1β, interleukin (IL)-1β; JNK, c-Jun N-terminal kinase; MMP, matrix metalloproteinase; OA, osteoarthritis. AbstractOsteoarthritis (OA) is a high-morbidity skeletal disease worldwide and the exact mechanisms underlying OA pathogenesis are not fully understood. Casein kinase 1 epsilon (CK1ε) is a serine/threonine protein kinase, but its relationship with OA is still unknown. We demonstrated that CK1ε was upregulated in articular cartilage of human patients with OA and mice with experimentally induced OA. Activity of CK1ε, demonstrated by analysis of phosphorylated substrates, was significantly elevated in interleukin (IL)-1β-induced OA-mimicking chondrocytes. CK1ε inhibitor or CK1ε short hairpin RNA (shRNA) partially blocked matrix metalloproteinase (MMP) expression by primary chondrocytes induced by IL-1β, and also inhibited cartilage destruction in knee joints of experimental OA model mice. Conversely, overexpression of CK1ε promoted chondrocyte catabolism. Previous studies indicated that CK1ε was involved in canonical Wnt/β-catenin signaling and noncanonical Wnt/c-Jun N-terminal kinase (JNK) signaling pathway. Interestingly, the activity of JNK but not β-catenin decreased after CK1ε knockdown in IL-1β-treated chondrocytes in vitro, and JNK inhibition reduced MMP expression in chondrocytes overexpressing CK1ε, which illustrated that CK1ε-mediated OA was based on JNK pathway. In conclusion, our results demonstrate that CK1ε promotes OA development, and inhibition of CK1ε could be a potential strategy for OA treatment in the future. K E Y W O R D S casein kinase 1 epsilon, c-Jun N-terminal kinase, osteoarthritis | 6467 HE Et al.

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“…It binds to Wnt ligand and then interacts with Dvl to promote the Dvl phosphorylation for downstream cascade reaction [19,20].…”

Section: Introductionmentioning

confidence: 99%

Wnt5b-induced PCP/JNK Activation Promotes PD-L1 Expression and the Malignant Phenotype of Non-small Cell Lung Cancer 

Wu¹,

Luo²,

Xie³

et al. 2020

Preprint

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Background: Wnt5b is noncanonical Wnt ligand, and programmed-death ligand 1 (PD-L1) is a targeted agent for immunotherapy, but the mechanism by which Wnt5b regulates PD-L1 expression in non-small cell lung cancer (NSCLC) is unclear. Methods: Wnt5b and PD-L1 expressions were detected in NSCLC specimens by immunohistochemistry. The interrelationship connecting Wnt5b with PD-L1 was verified using dual-luciferase assay, immunofluorescence, coimmunoprecipitation, western blot，real-time PCR and xenograft tumor model. Results: Wnt5b and PD-L1 expressions were positively correlated in NSCLC specimens. Five-year survival time in the group with their coexpression was significantly lower than that without coexpression. Under the effect of Wnt5b, Frizzled-3 (Fzd3) initiated Dishevellde-3 (Dvl-3) membrane recruitment via DEP domain by Dvl-3 phosphorylation, contributing to activate PCP/JNK signaling through the small GTPase Rac1, and then upregulate PD-L1 expression and promote the malignant phenotype of NSCLC in vivo and in vitro. After PD-L1 antibody treatment, Wnt5b induced tumor growth was inhibited significantly in xenograft tumor model. Conclusion: We demonstrate a new signal transduction pathway: Wnt5b initiates Dvl-3 membrane recruitment via DEP domain by Fzd3 so as to promote Rac1–PCP/JNK–PD-L1 pathway, which provides a potential target for clinical intervention and immunotherapy in lung cancer.

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CK1ε and p120‐catenin control Ror2 function in noncanonical Wnt signaling

Cited by 15 publications

References 59 publications

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Casein kinase 1 epsilon facilitates cartilage destruction in osteoarthritis through JNK pathway

Wnt5b-induced PCP/JNK Activation Promotes PD-L1 Expression and the Malignant Phenotype of Non-small Cell Lung Cancer

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CK1ε and p120‐catenin control Ror2 function in noncanonical Wnt signaling

Cited by 15 publications

References 59 publications

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Casein kinase 1 epsilon facilitates cartilage destruction in osteoarthritis through JNK pathway

Wnt5b-induced PCP/JNK&nbsp;Activation Promotes PD-L1&nbsp;Expression and the Malignant Phenotype of Non-small Cell Lung Cancer&nbsp;

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Wnt5b-induced PCP/JNK Activation Promotes PD-L1 Expression and the Malignant Phenotype of Non-small Cell Lung Cancer