Exo70 is an independent prognostic factor in colon cancer

Li, Xiao; Zheng, Kaifeng; Lv, Xia; Hou, Jihuan; Xu, Liang; Zhao, Yujie; Song, Fei; Fan, Yaqiong; Cao, Hanwei; Zhang, Wenqing; Hong, Xin; Zhan, Yan-yan; Hu, Tianhui

doi:10.1038/s41598-017-05308-x

Cited by 10 publications

(10 citation statements)

References 34 publications

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“…The function of EXO70 has been extensively studied in yeast, and mammals [3,10,11,12,13,14,15]. In plants, EXO70s have been proven to play diverse roles in regulating plant growth and coping with adverse biotic/abiotic stresses.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of the EXO70 Gene Family in Polyploid Wheat and Related Species

Zhao

Zhang

Wan

et al. 2018

IJMS

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The EXO70 gene family is involved in different biological processes in plants, ranging from plant polar growth to plant immunity. To date, analysis of the EXO70 gene family has been limited in Triticeae species, e.g., hexaploidy Triticum aestivum and its ancestral/related species. By in silico analysis of multiple Triticeae sequence databases, a total of 200 EXO70 members were identified. By homologue cloning approaches, 15 full-length cDNA of EXO70s were cloned from diploid Haynaldia villosa. Phylogenetic relationship analysis of 215 EXO70 members classified them into three groups (EXO70.1, EXO70.2, and EXO70.3) and nine subgroups (EXO70A to EXO70I). The distribution of most EXO70 genes among different species/sub-genomes were collinear, implying their orthologous relationship. The EXO70A subgroup has the most introns (at least five introns), while the remaining seven subgroups have only one intron on average. The expression profiling of EXO70 genes from wheat revealed that 40 wheat EXO70 genes were expressed in at least one tissue (leaf, stem, or root), of which 25 wheat EXO70 genes were in response to at least one biotic stress (stripe rust or powdery mildew) or abiotic stress (drought or heat). Subcellular localization analysis showed that ten EXO70-V proteins had distinct plasma membrane localization, EXO70I1-V showed a distinctive spotted pattern on the membrane. The 15 EXO70-V genes were differentially expressed in three tissue. Apart from EXO70D2-V, the remaining EXO70-V genes were in response to at least one stress (flg22, chitin, powdery mildew, drought, NaCl, heat, or cold) or phytohormones (salicylic acid, methyl jasmonate, ethephon, or abscisic acid) and hydrogen peroxide treatments. This research provides a genome-wide glimpse of the Triticeae EXO70 gene family and those up- or downregulated genes require further validation of their biological roles in response to biotic/abiotic stresses.

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Section: Introductionmentioning

confidence: 99%

Identification and Characterization of the EXO70 Gene Family in Polyploid Wheat and Related Species

Zhao

Zhang

Wan

et al. 2018

IJMS

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“…The exocyst mediates the tethering of secretory vesicles to the plasma membrane during exocytosis [9][10][11][12] . Recently, a role for the exocyst in cell migration and invasion has been reported [13][14][15][16][17][18][19][20][21][22][23][24] . The exocyst subunit Exo70 interacts with the Arp2/3 complex, a key nucleator of actin assembly, and enhances its binding to the nucleation-promoting factor WAVE2, thereby promoting lamellipodia formation and directionally cell migration 17,21,25 .…”

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confidence: 99%

ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

Mao

Zhan

et al. 2020

Nat Commun

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Increased expression of protein kinase ULK1 was reported to negatively correlate with breast cancer metastasis. Here we report that ULK1 suppresses the migration and invasion of human breast cancer cells. The suppressive effect is mediated through direct phosphorylation of Exo70, a key component of the exocyst complex. ULK1 phosphorylation inhibits Exo70 homooligomerization as well as its assembly to the exocyst complex, which are needed for cell protrusion formation and matrix metalloproteinases secretion during cell invasion. Reversely, upon growth factor stimulation, Exo70 is phosphorylated by ERK1/2, which in turn suppresses its phosphorylation by ULK1. Together, our study identifies Exo70 as a substrate of ULK1 that inhibits cancer metastasis, and demonstrates that two counteractive regulatory mechanisms are well orchestrated during tumor cell invasion.

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“…Additionally, we show that inhibition of Exo70 attenuates ERK1/2 phosphorylation, suggesting a role for Exo70 in feedback activation of ERK1/2 signaling. Notably, Exo70 mRNA and protein is overexpressed in colon cancer, in which both ERK1/2 and NT are also heavily implicated [68]. The exocyst complex has also been implicated in the epithelial-mesenchymal transition (EMT) in mammary epithelial cells [68, 69].…”

Section: Discussionmentioning

confidence: 99%

Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling

Rock

Song

et al. 2019

PLoS ONE

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Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal–regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal–regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal–regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates neurotensin secretion and extracellular signal–regulated kinase 1 and 2 signaling in human endocrine cells. Conversely, we show that overexpression of kinase suppressor of Ras 1 enhances neurotensin secretion and extracellular signal–regulated kinase 1 and 2 signaling. We also show that inhibition of extracellular signal–regulated kinase 2 and exocyst complex component 70, a substrate of extracellular signal–regulated kinase 2 and mediator of secretory vesicle exocytosis, potently inhibits basal and docosahexaenoic acid-stimulated neurotensin secretion, whereas overexpression of exocyst complex component 70 enhances basal and docosahexaenoic acid-stimulated neurotensin secretion. Together, our findings demonstrate a role for kinase suppressor of Ras 1 as a positive regulator of neurotensin secretion from human endocrine cells and indicate that this effect is mediated by the extracellular signal–regulated kinase 1 and 2 signaling pathway. Moreover, we reveal a novel role for exocyst complex component 70 in regulation of neurotensin vesicle exocytosis through its interaction with the extracellular signal–regulated kinase 1 and 2 signaling pathway.

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Exo70 is an independent prognostic factor in colon cancer

Cited by 10 publications

References 34 publications

Identification and Characterization of the EXO70 Gene Family in Polyploid Wheat and Related Species

Identification and Characterization of the EXO70 Gene Family in Polyploid Wheat and Related Species

ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling

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