LAMPs: Shedding light on cancer biology

Alessandrini, Federica; Pezzè, Laura; Ciribilli, Yari

doi:10.1053/j.seminoncol.2017.10.013

Cited by 101 publications

(88 citation statements)

References 152 publications

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“…Mechanistically, the lysosomal membrane proteins, LAMP1 and LAMP2, are estimated to contribute to about 50% of all lysosome membrane proteins [53]. LAMP2 has been shown to play roles in many diseases, but few such studies have been performed in liver cancer [16,54,55]. Here, we report that doxorubicin had similar effects on the expression levels of FAM215A and LAMP2.…”

Section: Discussionmentioning

confidence: 56%

“…Thus, it has been speculated that LAMP2A could be targeted as a novel treatment strategy for HCC [19]. Indeed, inhibition or genetic knockdown of LAMP2A resulted in the sensitization of tumor cells to Doxorubicin and radiation therapy [16]. Here, we found that FAM215A was affected by different doses of Doxorubicin ( Figure 3A).…”

Section: Fam215a Increases Hcc Progression and Drug Resistance Througmentioning

confidence: 61%

“…They are responsible for the disposal and recycling of worn-out and damaged cellular macromolecules and organelles, and the digestion of extracellular and foreign materials that are delivered to them by endocytosis, autophagy, and phagocytosis [15]. It has been well documented that during the process of cellular transformation and cancer progression, lysosomes exhibit changes in their localization, composition, and volume; moreover, lysozymes can, through the release of their enzymes, promote invasive growth, angiogenesis, and drug resistance [15,16]. Lysosomal-associated membrane protein (LAMP) 1 and 2 comprise nearly 50% of the lysosomal transmembrane, and they are essential for maintaining the structural integrity of the lysosomal compartment [15].…”

Section: Introductionmentioning

confidence: 99%

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Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

Huang

Lin

Cheng

et al. 2020

Cells

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Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Long non-coding (lnc) RNAs regulate complex cellular functions, such as cell growth, differentiation, metabolism, and metastasis. Although deregulation of lncRNA expression has been detected in HCC, many of the hepato-carcinogenesis-associated lncRNAs remain yet unidentified. Here, we aimed to investigate the involvement of a specific HCC-dysregulated lncRNA, FAM215A, and characterize its molecular regulation mechanism. We show for the first time that FAM215A is overexpressed in HCC, and its expression level correlates with tumor size, vascular invasion, and pathology stage. Overexpression of FAM215A accelerates cell proliferation and metastasis in HCC cells. According to Gene Expression Omnibus Dataset analysis, FAM215A is induced in doxorubicin (DOX)-resistant HCC cells. Overexpression of FAM215A increases DOX resistance in two HCC cell lines, and this is associated with enhanced expression of lysosome-associated membrane protein 2 (LAMP2). FAM215A interacts with LAMP2 to protect it from ubiquitination. Together, our results show that the lncRNA, FAM215A, is highly expressed in HCC, where it interacts with and stabilizes LAMP2 to increase tumor progression while decreasing doxorubicin sensitivity.

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Section: Discussionmentioning

confidence: 56%

Section: Fam215a Increases Hcc Progression and Drug Resistance Througmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

Huang

Lin

Cheng

et al. 2020

Cells

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“…3) [25]. The selected factors affecting the process of LNM and the possible candidates for further drug development are listed in Table 4 [26][27][28][29][30][31][32][33].…”

Section: Its Role Referencesmentioning

confidence: 99%

New therapeutic approaches in the treatment of node-positive cervical cancer patients based on molecular targets: a systematic review

et al. 2019

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Cervical uterine cancer is the second most frequent female cancer worldwide and a substantial burden for low-income societies and the patients themselves. Understanding the molecular mechanisms of metastasis permits the development of therapies that limit tumor progression, as well as providing health and social benefits. Pathomorphology is still the basis of research and a reference standard for molecular analysis. The aim of our study was to research and critically evaluate clinical trials that use new oncological approaches for node-positive cervical cancer to gain an insight into the molecular mechanisms of tumor metastasis. Inclusion criteria: node-positive disease at baseline; at least a first phase clinical study comprising adult female patients; novel clinical approach (e.g., radiotherapy, immunotherapy, targeted therapy, vaccines, radiosurgery); histologic measurement of treatment efficacy (preferably lymph node ultrastaging); and publications in English language only. Information sources: US Clinical trials registry, EU Clinical trials register, ISRCTN registry, and Ovid, EBSCO and Cochrane Collaboration databases. Access dates: from January 2010 to April 2018. Exclusions: Abstracts that did not meet the inclusion criteria or with unreliable data. We collected complete data (e.g., the entire publication associated with included abstracts, heterogeneity examination of individual studies, and validity measurement of the statistical methods used). Results were analyzed in relation to the most recent understanding of the pathogenesis of cervical cancer metastasis. We proposed a possible direction for drug treatment of epithelial tumors based on the mechanisms of metastasis.

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“…Lysosomal associated membrane proteins (LAMPs) family is characterized by an evolutionary-conserved membrane-proximal LAMP domain and composed of five known members: LAMP1, LAMP2, LAMP3, LAMP4 and LAMP5. 9 LAMP2 has been well documented in a variety of cellular processes including autophagy, specifically chaperone-mediated autophagy (CMA), a process that targets specific proteins to degradation by lysosomes. 10 LAMP2 can affect the lysosomes localization and the autophagic flux, and LAMP2 deficiency was responsible for Azacytidine resistance in MDS/AML cells.…”

Section: Introductionmentioning

confidence: 99%

<p>PHLPP Sensitizes Multiple Myeloma Cells to Bortezomib Through Regulating LAMP2</p>

Liu

et al. 2020

OTT

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Introduction: Treatment of bortezomib (BTZ) improves the clinical outcomes of patients with multiple myeloma (MM). However, primary resistance and acquired resistance to BTZ frequently develop in patients with MM. PH domain leucine-rich repeat protein phosphatase (PHLPP) plays an important role in chemoresistance in a number of cancers. However, the role of PHLPP on MM remains unclear. In this study, we investigated the role of PHLPP in BTZ-resistant MM cells. Methods: BrdU assays, immunoprecipitation, flow cytometry analyses, and immunofluorescence assays were performed. Results: PHLPP and lysosome-associated membrane protein 2 (LAMP2) levels were downregulated in BTZ-resistant MM cells compared with BTZ-sensitive MM cells, accompanied by inactivation of autophagy pathway evaluated by a reduction in Beclin1, Atg5 and LC3B and increase in p62. Gain-and loss-of-function experiments revealed that PHLPP partially re-sensitized MM cells to BTZ. In addition, PHLPP overexpression increased whereas PHLPP knockdown reduced LAMP2 expression, subsequently regulating the autophagy pathway in MM cells. Further findings demonstrated that LAMP2 knockdown reversed PHLPP-mediated cell apoptosis and autophagy activation in MM cells. Conclusion: This study demonstrated that PHLPP is a potential strategy for overcoming BTZ resistance in patients with MM.

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LAMPs: Shedding light on cancer biology

Cited by 101 publications

References 152 publications

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

New therapeutic approaches in the treatment of node-positive cervical cancer patients based on molecular targets: a systematic review

<p>PHLPP Sensitizes Multiple Myeloma Cells to Bortezomib Through Regulating LAMP2</p>

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