Rab34 regulates adhesion, migration, and invasion of breast cancer cells

Sun, Lixiang; Xu, Xiaohui; Chen, Yongjun; Zhou, Yüxia; Tan, Renxiang; Qiu, Hantian; Jin, Liting; Zhang, Wenyi; Fan, Rong; Hong, Wanjin; Wang, Tuanlao

doi:10.1038/s41388-018-0202-7

Cited by 43 publications

(40 citation statements)

References 54 publications

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“…Moreover, the observation that CLB2 deletion (suppressing effect) opposes that of CLB5 (deletion enhancing; see above Fig. 6D, 1-0-0) has been previously described in the context of loss of the S-phase checkpoint [263] ; (8) SKY1/SRPK1 (serine-arginine rich serine-threonine kinase), which is overexpressed in glioma, and prostate, breast, and lung cancer [207] ; (9) SNC2/VAMP8 , which functions in fusion of Golgi-derived vesicles with the plasma membrane and is overexpressed in glioma and breast cancer [208,209] ; (10) YPT6/RAB34 , which functions in fusion of endosome-derived vesicles with the late Golgi and is overexpressed in glioma, breast cancer, and hepatocellular carcinoma [211-213]; (11) TOP1/TOP1/TOP1MT , Topoisomerase I, which has increased copy number in pancreatic and bile duct cancer [210]; (12) ALD6 , which encodes cytosolic aldehyde dehydrogenase, and was a deletion suppressor for both gemcitabine and cytarabine, having multiple homologs that were OES ( ALDH1A1 , ALDH1A2 , ALDH1B1 , and ALDH7A1. ALDH1B1 ).…”

Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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10Knowledge about synthetic lethality can be applied to enhance the efficacy of 11 anti-cancer therapies in individual patients harboring genetic alterations in their cancer 12 that specifically render it vulnerable. We investigated the potential for high-resolution 13 phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, 14 comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine 15 and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures 16 yet distinct anti-tumor efficacy. Human deoxycytidine kinase (dCK) was conditionally 17 expressed in the S. cerevisiae genomic library of knockout and knockdown (YKO/KD) 18 strains, to globally and quantitatively characterize differential drug-gene interaction for 19 gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, 20 histone modification, chromatin remodeling, and apoptosis-related processes influence 21 gemcitabine specifically, while drug-gene interaction specific to cytarabine was less 22 enriched in Gene Ontology. Processes having influence over both drugs were DNA 23 repair and integrity checkpoints and vesicle transport and fusion. Non-GO-enriched 24 genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics 25 data were integrated to identify yeast-human homologs with correlated differential gene 26 2 expression and drug-efficacy, thus providing a unique resource to predict whether 27 differential gene expression observed in cancer genetic profiles are causal in tumor-28 specific responses to cytotoxic agents. 29 30 Keywords: 31 yeast phenomics, gene-drug interaction, genetic buffering, quantitative high 32 throughput cell array phenotyping (Q-HTCP), cell proliferation parameters (CPPs), 33 gemcitabine, cytarabine, recursive expectation-maximization clustering (REMc), 34 pharmacogenomics 35 36 Introduction: 37Genomics has enabled targeted therapy aimed at cancer driver genes and 38 oncogenic addiction [1], yet traditional cytotoxic chemotherapeutic agents remain among 39 the most widely used and efficacious anti-cancer therapies [2]. Changes in the genetic 40 network underlying cancer can produce vulnerabilities to cytotoxic chemotherapy that 41 further influence the therapeutic window and provide additional insight into their 42 mechanisms of action [3,4]. A potential advantage of so-called synthetic lethality-based 43 treatment strategies is that they could have efficacy against passenger gene mutation or 44 compensatory gene expression, while classic targeted therapies are directed primarily at 45 driver genes ( Fig. 1A). Quantitative high throughput cell array phenotyping of the yeast 46 knockout and knockdown libraries provides a phenomic means for systems level, high- 47resolution modeling of gene interaction [5][6][7][8][9], which is applied here to predict cancer-48 relevant drug-gene interaction through integration with cancer pharmacogenomics 49 resources ( Fig. 1B). 50Nucleoside analogs include a diverse group of co...

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Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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“…30 Previous results uncovered the role of Rab34 in migration and invasion of breast cancer cells and its involvement in cancer metastasis. 15 In spite of these findings, the function of RAB34 in NSCLC was unclear. In our study, the expression of RAB34 was verified to be up-regulated in NSCLC tissues and cells and is positively regulated by PVT1, meantime, negatively regulated by miR-148.…”

Section: Discussionmentioning

confidence: 99%

“…RAB34 is belonging to the RAB family that are associated with many cancers. 15 A tumor suppressor-folliculin directs the formation of Rab34-RILP complex to regulate the nutrientdependent dynamic distribution of lysosomes. 16 A previous study showed that RAB34 targeted miR-9 was up-regulated in human gastric carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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<p>PVT1 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer via Regulating miR-148/RAB34 Signal Axis</p>

Shen

Jin

et al. 2020

OTT

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It has been verified that long non-coding RNAs (lncRNAs) play critical roles in the development of human cancers. Increasing evidence indicates that lncRNA human plasmacytoma variant translocation1 (PVT1) was dysregulated in non-small cell lung cancer (NSCLC) which is the leading cause of cancer-related death. However, the precise mechanism underlying the effect of PVT1 remains elusive. Our research focused on the correlation of PVT1 to miR-148 and RAB34 in NSCLC. Methods: The quantitative real-time PCR (qRT-PCR) and western blot assay were used to detect gene and protein expression in NSCLC tissues and cells. CCK8, colony formation, transwell and wound healing assays were performed to evaluate the cell function of NSCLC cells. Dual-luciferase activity assay and RNA pull down assays were performed to verify the interaction between miR-148 and its targets. A xenograft test was conducted to detect the impact of RAB34 on tumor development in vitro. Results: In NSCLC tissues and cells, PVT1 and RAB34 were up-regulated, and miR-148 was down-regulated. Overexpression of PVT1 was capable of promoting NSCLC cell proliferation and migration which could be reversed by miR-148 restoration or RAB34 knock down. Also, our data firstly determined that the down-regulation of RAB34 had inhibitor effects while the up-regulation of RAB34 had promotive effects on tumor growth in vitro and in vivo. Conclusion: Those findings indicated that the signal pathway PVT1/miR-148/RAB34 play critical roles in the progression of NSCLC could be proposed in NSCLC as a possible diagnosis or therapeutic targets.

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“…The post‐translational modification of K‐Ras occurs adjacent to switches 1 and 2, altering the conformation of the switch regions and subsequently impairing effector interactions. Finally, Rab34 is phosphorylated by Src kinase at Y247 within the C‐terminal hypervariable region (HVD, residues 218‐259) 10 . Rab34 is localized to membrane ruffles and its overexpression is associated with aggressive breast cancer 10 .…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of Rab GTPases in the regulation of membrane trafficking

Waschbüsch

Khan

2020

Traffic

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Rab GTPases are master regulators of membrane trafficking in eukaryotic cells. Phosphorylation of Rab GTPases was characterized in the 1990s and there have been intermittent reports of its relevance to Rab functions. Phosphorylation as a regulatory mechanism has gained prominence through the identification of Rabs as physiological substrates of leucine‐rich repeat kinase 2 (LRRK2). LRRK2 is a Ser/Thr kinase that is associated with inherited and sporadic forms of Parkinson disease. In recent years, numerous kinases and their associated signaling pathways have been identified that lead to phosphorylation of Rabs. These emerging studies suggest that serine/threonine and tyrosine phosphorylation of Rabs may be a widespread and under‐appreciated mechanism for controlling their membrane trafficking functions. Here we survey current knowledge of Rab phosphorylation and discuss models for how this post‐translational mechanism exerts control of membrane trafficking.

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Rab34 regulates adhesion, migration, and invasion of breast cancer cells

Cited by 43 publications

References 54 publications

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

<p>PVT1 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer via Regulating miR-148/RAB34 Signal Axis</p>

Phosphorylation of Rab GTPases in the regulation of membrane trafficking

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