Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Wu, Ping-Hsiu; Onodera, Yasuhito; Giaccia, Amato J.; Le, Quynh‐Thu; Shimizu, Satoru; Shirato, Hiroki; Nam, Jwa Min

doi:10.1038/s42003-020-01339-9

Cited by 28 publications

(25 citation statements)

References 71 publications

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“…Instead, repurposing FDA approved drugs with P-glycoprotein inhibitory properties might prove more useful ( Lai et al, 2020 ). Furthermore, recent lines of evidence show that the mechanism by which some cancer cells become resistant to radiation is associated with lysosomal exocytosis, which is enhanced by the activity of Arl8b ( Wu et al, 2020 ). High levels of Arl8b and BORC subunit genes is indeed correlated with a poor prognosis in breast cancer, and knockdown of these genes decreases the survival and invasiveness of cancer cells.…”

Section: Lysosomal Dysfunctions Related Diseases and Therapeuticsmentioning

confidence: 99%

A Compendium of Information on the Lysosome

Bouhamdani

Comeau

Turcotte

2021

Front. Cell Dev. Biol.

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For a long time, lysosomes were considered as mere waste bags for cellular constituents. Thankfully, studies carried out in the past 15 years were brimming with elegant and crucial breakthroughs in lysosome research, uncovering their complex roles as nutrient sensors and characterizing them as crucial multifaceted signaling organelles. This review presents the scientific knowledge on lysosome physiology and functions, starting with their discovery and reviewing up to date ground-breaking discoveries highlighting their heterogeneous functions as well as pending questions that remain to be answered. We also review the roles of lysosomes in anti-cancer drug resistance and how they undergo a series of molecular and functional changes during malignant transformation which lead to tumor aggression, angiogenesis, and metastases. Finally, we discuss the strategy of targeting lysosomes in cancer which could lead to the development of new and effective targeted therapies.

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Section: Lysosomal Dysfunctions Related Diseases and Therapeuticsmentioning

confidence: 99%

A Compendium of Information on the Lysosome

Bouhamdani

Comeau

Turcotte

2021

Front. Cell Dev. Biol.

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“…Moreover, PLK1 has been shown to play a role in TNBC progression, metastasis, and resistance [39][40][41]. A study by Wu et al (2020) showed that lysosomal trafficking mediated by ARL8B promotes invasion of BC and is associated with poor survival outcomes [42], which was also confirmed by another study in both BC and prostate cancer [43].…”

Section: Discussionmentioning

confidence: 85%

TBC1D9: An Important Modulator of Tumorigenesis in Breast Cancer

Kothari

Clemenceau

Ouellette

et al. 2021

Cancers

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Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.

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“…Previous studies revealed that SAFB2 could be a biomarker in breast and renal cell cancers [ 42 , 43 ]. ARL8B is a pivotal regulative gene of lysosomal location; a prior study demonstrated that the expression of ARL8B is closely correlated with the prognosis of breast cancer patients [ 44 ]. Knockdown of VPS18 could repress the progression of glioma through sponging miR-370 [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of an Autophagy-Related Prognostic Model for Osteosarcoma Patients

Lei

et al. 2021

Journal of Oncology

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While the prognostic value of autophagy-related genes (ARGs) in OS patients remains scarcely known, increasing evidence is indicating that autophagy is closely associated with the development and progression of osteosarcoma (OS). Therefore, we explored the prognostic value of ARGs in OS patients and illuminate associated mechanisms in this study. When the OS patients in the training/validation cohort were stratified into high- and low-risk groups according to the risk model established using least absolute shrinkage and selection operator (LASSO) regression analysis, we observed that patients in the low-risk group possessed better prognosis ( P < 0.0001 ). Univariate/Multivariate COX regression and subgroup analysis demonstrated that the ARGs-based risk model was an independent survival indicator for OS patients. The nomogram incorporating the risk model and clinical features exhibited excellent prognostic accuracy. GO, KEGG, and GSVA analyses collectively indicated that bone development-associated pathway mediated the contribution of ARGs to the malignance of OS. Immune infiltration analysis suggested the potential pivotal role of macrophage in OS. In summary, the risk model based on 12 ARGs possessed potent capacity in predicting the prognosis of OS patients. Our work may assist clinicians to map out more reasonable treatment strategies and facilitate individual-targeted therapy in osteosarcoma.

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Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

Cited by 28 publications

References 71 publications

A Compendium of Information on the Lysosome

A Compendium of Information on the Lysosome

TBC1D9: An Important Modulator of Tumorigenesis in Breast Cancer

Construction and Validation of an Autophagy-Related Prognostic Model for Osteosarcoma Patients

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