Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B

Zhang, Zhonghua; Gao, Xuefeng; Ma, Qinghua; Yu, Zhiyong; Huang, Shuhong

doi:10.1016/j.canlet.2022.215629

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…The tumor-promoting effect of Rab8A has been involved in various physiological activities and signaling pathways [ 7 ]. In this study, we discovered that Rab8A was highly expressed in esophagus cancer samples, and knockdown of Rab8A suppressed the growth, migration, and invasion as well as induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the effect of Rab8A in cancer has been reported. For example, Rab8A has been found to promote breast cancer progression by elevating surface expression of tropomyosin-related kinase B [ 7 ]; Rab8A was reported to promote the growth and metastasis of cervical cancer [ 8 ]. However, the function and molecular mechanism of Rab8A in esophagus cancer has not been revealed.…”

Section: Introductionmentioning

confidence: 99%

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Transcription Activation of Rab8A by PEA3 Augments Progression of Esophagus Cancer by Activating the Wnt/β-Catenin Signaling Pathway

et al. 2023

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Background. Rab8A has been reported as an oncogenic gene in breast and cervical cancer. However, the function and molecular mechanism of Rab8A in esophagus cancer has not been reported. Methods. Rab8A expression was detected by qPCR and western blotting assays, small interference RNA (siRNA) was applied to reduce Rab8A expression, and the biological behaviors of esophagus cancer cells were estimated by cell counting kit-8, colony formation, and transwell and western blotting assays. The transcriptional factor of Rab8A was verified by dual-luciferase assay and chromatin immunoprecipitation assay. The protein expression of key genes in the Wnt/β-catenin signaling pathway was determined by western blotting assay. M435-1279 was used to suppress the Wnt/β-catenin signaling pathway. Results. A significant increase of Rab8A expression has been found in esophagus cancer cells. Knockdown of Rab8A suppressed the viability, colony formation, migration, and invasion abilities of esophagus cancer cells and induced apoptosis. PEA3 transcriptionally regulated Rab8A expression and promoted the viability, colony formation, migration, and invasion abilities of esophagus cancer cells and blocked apoptosis, which were diminished by si-Rab8A transfection. Additionally, the expression levels of key genes related to the Wnt/β-catenin signaling pathway were strengthened by PEA3 overexpression, which were reduced by si-Rab8A transfection. M435-1279 treatment significantly reduced the viability and colony formation of esophagus cancer cells. Conclusions. The data showed that Rab8A was transcriptionally regulated by PEA3 and promoted the malignant behaviors of esophagus cancer cells by activating the Wnt/β-catenin pathway. The above results indicated that Rab8A may be considered as a promising biomarker for diagnosis and precision treatment in esophagus cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcription Activation of Rab8A by PEA3 Augments Progression of Esophagus Cancer by Activating the Wnt/β-Catenin Signaling Pathway

et al. 2023

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“…In neurons, the neurotrophin receptors, Tropomyosin-related kinase A, B and C (TrkA, TrkB and TrkC), are synthesized in the cell body and transported to axonal PM over long distances. Interestingly, TrkB has been shown to interact with Rab8a in coimmunoprecipitation studies and knockdown of Rab8a also reduced PM localization of TrkB, without increasing internalization of TrkB [85]. Rab8 is present in axons and dendrites of neurons at early developmental stages and antisense oligonucleotide-mediated reduction in Rab8 expression inhibits membrane traffic and blocks maturation of neurons [86].…”

Section: Discussionmentioning

confidence: 99%

Controlled Plasma Membrane Delivery of FGFR1 and Modulation of Signaling by a Novel Regulated Anterograde RTK Transport Pathway

Hinsch,

Venkata,

Hsu

et al. 2023

Cancers

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How human FGFR1 localizes to the PM is unknown. Currently, it is assumed that newly synthesized FGFR1 is continuously delivered to the PM. However, evidence indicates that FGFR1 is mostly sequestered in intracellular post-Golgi vesicles (PGVs) under normal conditions. In this report, live-cell imaging and total internal reflection fluorescence microscopy (TIRFM) were employed to study the dynamics of these FGFR1-positive vesicles. We designed recombinant proteins to target different transport components to and from the FGFR1 vesicles. Mouse embryoid bodies (mEBs) were used as a 3D model system to confirm major findings. Briefly, we found that Rab2a, Rab6a, Rab8a, RalA and caveolins are integral components of FGFR1-positive vesicles, representing a novel compartment. While intracellular sequestration prevented FGFR1 activation, serum starvation and hypoxia stimulated PM localization of FGFR1. Under these conditions, FGFR1 C-terminus acts as a scaffold to assemble proteins to (i) inactivate Rab2a and release sequestration, and (ii) assemble Rab6a for localized activation of Rab8a and RalA-exocyst to deliver the receptor to the PM. This novel pathway is named Regulated Anterograde RTK Transport (RART). This is the first instance of RTK regulated through control of PM delivery.

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“…In BC, RAB8 regulates the exocytosis of MT1-MMP, which promotes collagen degradation and cell invasion ( Bravo-Cordero et al, 2007 ). Recently, Liu et al showed that RAB8A is upregulated in BC ( Liu et al, 2022 ). Moreover, RAB8A promotes the surface expression of tropomyosin-related kinase B (TRKB), which leads to the proliferation, migration and invasion of BC cells, through activation of the AKT and extracellular signal-regulated kinase (ERK) 1/2 signaling pathways ( Liu et al, 2022 ).…”

Section: Secretion/exocytosismentioning

confidence: 99%

Membrane trafficking alterations in breast cancer progression

Ferreira,

Castanheira,

Escrevente

et al. 2024

Front. Cell Dev. Biol.

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Breast cancer (BC) is the most common type of cancer in women, and remains one of the major causes of death in women worldwide. It is now well established that alterations in membrane trafficking are implicated in BC progression. Indeed, membrane trafficking pathways regulate BC cell proliferation, migration, invasion, and metastasis. The 22 members of the ADP-ribosylation factor (ARF) and the >60 members of the rat sarcoma (RAS)-related in brain (RAB) families of small GTP-binding proteins (GTPases), which belong to the RAS superfamily, are master regulators of membrane trafficking pathways. ARF-like (ARL) subfamily members are involved in various processes, including vesicle budding and cargo selection. Moreover, ARFs regulate cytoskeleton organization and signal transduction. RABs are key regulators of all steps of membrane trafficking. Interestingly, the activity and/or expression of some of these proteins is found dysregulated in BC. Here, we review how the processes regulated by ARFs and RABs are subverted in BC, including secretion/exocytosis, endocytosis/recycling, autophagy/lysosome trafficking, cytoskeleton dynamics, integrin-mediated signaling, among others. Thus, we provide a comprehensive overview of the roles played by ARF and RAB family members, as well as their regulators in BC progression, aiming to lay the foundation for future research in this field. This research should focus on further dissecting the molecular mechanisms regulated by ARFs and RABs that are subverted in BC, and exploring their use as therapeutic targets or prognostic markers.

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Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B

Cited by 6 publications

References 45 publications

Transcription Activation of Rab8A by PEA3 Augments Progression of Esophagus Cancer by Activating the Wnt/β-Catenin Signaling Pathway

Transcription Activation of Rab8A by PEA3 Augments Progression of Esophagus Cancer by Activating the Wnt/β-Catenin Signaling Pathway

Controlled Plasma Membrane Delivery of FGFR1 and Modulation of Signaling by a Novel Regulated Anterograde RTK Transport Pathway

Membrane trafficking alterations in breast cancer progression

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