CLIP‐170 spatially modulates receptor tyrosine kinase recycling to coordinate cell migration

Zaoui, Kossay; Duhamel, Stéphanie; Parachoniak, Christine A.; Park, Morag

doi:10.1111/tra.12629

Cited by 6 publications

(4 citation statements)

References 62 publications

(146 reference statements)

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“…CLIP1 mediates microtubule capture through the interaction with RHO GTPases activating the IQGAPs pathway (21). Microtubule capture may be linked to wound healing through stimulation of cell migration and fibroblasts (22,23) and is involved in T Cell regulation (23)(24)(25). This finding is similar to previous murine findings that demonstrated the upregulation of fibrosis linked genes in the late stages of S. japonicum infection (5,6,26).…”

Section: Discussionsupporting

confidence: 84%

Transcriptome analysis of peripheral blood ofSchistosoma mansoniinfected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology

Namulondo¹,

Nyangiri²,

Kimuda³

et al. 2023

Preprint

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Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all Schistosoma species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10 - 15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response.

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Section: Discussionsupporting

confidence: 84%

Transcriptome analysis of peripheral blood ofSchistosoma mansoniinfected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology

Namulondo¹,

Nyangiri²,

Kimuda³

et al. 2023

Preprint

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“…Rlip depletion has been shown to inhibit PIK3CA in other cancers [ 55 , 86 , 87 ], and both Rlip and PIK3CA are known to regulate CDE [ 55 , 88 , 89 , 90 ]. Indeed, signaling initiated by growth factors including the EGF family (including Her3) and HGF is known to be broadly regulated by endocytosis of the receptor/ligand complex by CDE [ 91 , 92 ], and thus also by Rlip. The AP2 clathrin adapter protein of the clathrin-coated vesicles binds Rlip [ 93 ], and the ATPase and GS–E (glutathione–electrophile conjugate) transport activity of Rlip is coupled to CDE.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Ω-6 Fatty Acids through Increased 4-HNE in Breast Cancer Cells

Bose

Hindle

Lee

et al. 2021

Cancers

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Her2-amplified breast cancers resistant to available Her2-targeted therapeutics continue to be a challenge in breast cancer therapy. Dox is the mainstay of chemotherapy of all types of breast cancer, but its usefulness is limited by cumulative cardiotoxicity. Because oxidative stress caused by dox generates the pro-apoptotic Ω-6 PUFA metabolite 4-hydroxynonenal (4-HNE), we surmised that Ω-6 PUFAs would increase the effectiveness of dox chemotherapy. Since the mercapturic acid pathway enzyme RALBP1 (also known as RLIP76 or Rlip) that limits cellular accumulation of 4-HNE also mediates dox resistance, the combination of Ω-6 PUFAs and Rlip depletion could synergistically improve the efficacy of dox. Thus, we studied the effects of the Ω-6 PUFA arachidonic acid (AA) and Rlip knockdown on the antineoplastic activity of dox towards Her2-amplified breast cancer cell lines SK-BR-3, which is sensitive to Her2 inhibitors, and AU565, which is resistant. AA increased lipid peroxidation, 4-HNE generation, apoptosis, cellular dox concentration and dox cytotoxicity in both cell lines while sparing cultured immortalized cardiomyocyte cells. The known functions of Rlip including clathrin-dependent endocytosis and dox efflux were inhibited by AA. Our results support a model in which 4-HNE generated by AA overwhelms the capacity of Rlip to defend against apoptosis caused by dox or 4-HNE. We propose that Ω-6 PUFA supplementation could improve the efficacy of dox or Rlip inhibitors for treating Her2-amplified breast cancer.

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“…CLIP-170, a +TIP MAP, is widely known to regulate cellular trafficking through microtubules ( Chen Y. et al, 2019 ). Likewise, CLIP-170 has been reported to regulate the recycling of Met receptor tyrosine kinase (Met RTK) ( Zaoui et al, 2019 ). An internalization of Met RTK is essential for RTK degradation and recycling to the cell surface ( Barrow-McGee and Kermorgant, 2014 ).…”

Section: Microtubule-associated Proteins and Their Role In Cancer Met...mentioning

confidence: 99%

Emerging role of microtubule-associated proteins on cancer metastasis

Wattanathamsan

Pongrakhananon

2022

Front. Pharmacol.

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The major cause of death in cancer patients is strongly associated with metastasis. While much remains to be understood, microtubule-associated proteins (MAPs) have shed light on metastatic progression’s molecular mechanisms. In this review article, we focus on the role of MAPs in cancer aggressiveness, particularly cancer metastasis activity. Increasing evidence has shown that a growing number of MAP member proteins might be fundamental regulators involved in altering microtubule dynamics, contributing to cancer migration, invasion, and epithelial-to-mesenchymal transition. MAP types have been established according to their microtubule-binding site and function in microtubule-dependent activities. We highlight that altered MAP expression was commonly found in many cancer types and related to cancer progression based on available evidence. Furthermore, we discuss and integrate the relevance of MAPs and related molecular signaling pathways in cancer metastasis. Our review provides a comprehensive understanding of MAP function on microtubules. It elucidates how MAPs regulate cancer progression, preferentially in metastasis, providing substantial scientific information on MAPs as potential therapeutic targets and prognostic markers for cancer management.

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CLIP‐170 spatially modulates receptor tyrosine kinase recycling to coordinate cell migration

Cited by 6 publications

References 62 publications

Transcriptome analysis of peripheral blood ofSchistosoma mansoniinfected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology

Transcriptome analysis of peripheral blood ofSchistosoma mansoniinfected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology

Anticancer Activity of Ω-6 Fatty Acids through Increased 4-HNE in Breast Cancer Cells

Emerging role of microtubule-associated proteins on cancer metastasis

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