PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization

Li, Meng-Yen; Peng, Wen-Hsin; Wu, Chien‐Hsun; Chang, Ya-Min; Lin, Yuling; Chang, Geen-Dong; Wu, Han‐Chung; Chen, Guang-Chao

doi:10.1038/s41388-019-0948-6

Cited by 29 publications

(20 citation statements)

References 64 publications

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“…Bands at western blot were observed in the case of LmForminA at higher molecular weight than predicted, indicating there might be a post-translation modification (fig. 1C) similar observation recorded in DAAM1, FMNL2 in mammalian cells (Li et al, 2019). However, further studies are needed to confirm the post-translational modifications.…”

Section: Discussionsupporting

confidence: 85%

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

Kushwaha

Seth

Jijumon

et al. 2021

Preprint

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Formin proteins regulate actin dynamics, are conserved throughout the eukaryotes cells. They play an important role in cell adhesion, motility, vesicular trafficking, and cytokinesis. Formins from class Kinetoplastida which includes infective organisms such as Leishmania and Trypanosoma not characterized to date, even though they are shown to be important in other protozoan parasites. The protozoan parasite Leishmania major (Lm) has two homologous formin proteins; LmForminA and LmForminB. Our study showed that LmForminA and LmForminB are expressed at RNA and protein levels in L. major cells. LmForminA and LmForminB are localized in the cytosol in patchy distribution patterns. LmForminA and LmForminB puncta also colocalize with the actin patches. The biochemical properties of L. major formins divulge that both formins are potent actin nucleator. LmForminA and LmForminB bind with the actin filament and have actin-bundling activity. We have also observed that formin inhibitor SMIFH2 influences the growth and physiology of L. major cells indicating formins are important for the Leishmania parasite.

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Section: Discussionsupporting

confidence: 85%

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

Kushwaha

Seth

Jijumon

et al. 2021

Preprint

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“…PTPN3 inhibited Src activity and Src-mediated phosphorylation of Tyr652 on DAAM1. Reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulated actin dynamics and lung cancer invasiveness [75]. The characterization of new genetic alterations is essential to assign effective personalized therapies in NSCLC; furthermore, finding stratification biomarkers is essential for successful personalized therapies.…”

Section: Lung Cancermentioning

confidence: 99%

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Martellucci

Clementi

Sabetta

et al. 2020

Cancers

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Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression

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“…Of all of the other family members (FYN, YES, BLK, YRK, FGR, HCK, LCK, and LYN) cSrc is the most often associated with cancer progression ( 35 ). This kinase has been associated with migration and invasion of multiple malignancies through the regulation of actomyosin contraction, actin polymerization ( 36 ), and ECM proteolysis ( 37 ). In glioblastomas, SFKs play an essential role in events related to motility and disruption of ECM.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells

2021

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Glioblastomas are the most common and aggressive primary brain tumors in adults, and patients with glioblastoma have a median survival of 15 months. Some alternative therapies, such as Src family kinase inhibitors, have failed presumably because other signaling pathways compensate for their effects. In the last ten years, it has been proven that sex hormones such as progesterone (P4) can induce growth, migration, and invasion of glioblastoma cells through its intracellular progesterone receptor (PR), which is mostly known for its role as a transcription factor, but it can also induce non-genomic actions. These non-classic actions are, in part, a consequence of its interaction with cSrc, which plays a significant role in the progression of glioblastomas. We studied the relation between PR and cSrc, and its effects in human glioblastoma cells. Our results showed that P4 and R5020 (specific PR agonist) activated cSrc protein since both progestins increased the p-cSrc (Y416)/cSrc ratio in U251 and U87 human glioblastoma derived cell lines. When siRNA against the PR gene was used, the activation of cSrc by P4 was abolished. The co-immunoprecipitation assay showed that cSrc and PR interact in U251 cells. P4 treatment also promoted the increase in the p-Fak (Y397) (Y576/577)/Fak and the decrease in p-Paxillin (Y118)/Paxillin ratio, which are significant components of the focal adhesion complex and essential for migration and invasion processes. A siRNA against cSrc gene blocked the increase in the p-Fak (Y576/Y577)/Fak ratio and the migration induced by P4, but not the decrease in p-Paxillin (Y118)/Paxillin ratio. We analyzed the potential role of cSrc over PR phosphorylation in three databases, and one putative tyrosine residue in the amino acid 87 of PR was found. Our results showed that P4 induces the activation of cSrc protein through its PR. The latter and cSrc could interact in a bidirectional mode for regulating the activity of proteins involved in migration and invasion of glioblastomas.

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PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization

Cited by 29 publications

References 64 publications

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells

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