Identification of a Novel Mutation of<i>LAMB3</i>Gene in a Lybian Patient with Hereditary Epidermolysis Bullosa by Whole Exome Sequencing

Laroussi, Nadia; Messaoud, Olfa; Chargui, Mariem; Fayala, Chaima Ben; Elahlafi, Abdelaziz; Mokni, M.; Bashamboo, Anu; McElreavey, Kenneth; Boubaker, Mohamed Samir; Yacoub‐Youssef, Houda; Abdelhak, Sonia

doi:10.5021/ad.2017.29.2.243

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…The LAMB3 mutation found in the siblings was recently reported in a Libyan patient with JEB (6). The mutation was predicted to abolish the donor splice site and lead to an aberrant transcript with an in-frame skipping of 82 nucleotides, but the precise consequences have not been disclosed (6). The current cases demonstrate that residual laminin 332 expression accounts for a generalized-intermediate JEB phenotype.…”

Section: Discussionmentioning

confidence: 81%

Successful Multidisciplinary Treatment of Chronic Facial Wounds in Junctional Epidermolysis Bullosa

Reimer

Laszig²,

Pfeiffer³

et al. 2018

Acta Derm Venerol

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Section: Discussionmentioning

confidence: 81%

Successful Multidisciplinary Treatment of Chronic Facial Wounds in Junctional Epidermolysis Bullosa

Reimer

Laszig²,

Pfeiffer³

et al. 2018

Acta Derm Venerol

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“…LAMB3 encodes one of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. While LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, its mechanism of action in pancreatic cancer has not been investigated previously 9–11 .…”

Section: Introductionmentioning

confidence: 99%

LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway

et al. 2019

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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. In addition, LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, but the role and mechanism of LAMB3 in PDAC have not been previously determined. Herein, we tentatively investigated the role of LAMB3 in the malignant biological behavior of PDAC. In this study, we demonstrated that LAMB3 is upregulated in PDAC. Inhibition of LAMB3 abrogated the tumorigenic outcomes of PI3K/Akt signaling pathway activation, including those involving cell cycle arrest, cell apoptosis, proliferation, invasion and migration in vitro, and tumor growth and liver metastasis in vivo. Our results showed that LAMB3 could mediate cell cycle arrest and apoptosis in PDAC cells and alter the proliferative, invasive, and metastatic behaviors of PDAC by regulating the PI3K/Akt signaling pathway. LAMB3 may be a novel therapeutic target for the treatment of PDAC in the future.

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“…LAMB3 encodes one of the three subunits of laminin-332 (LM-332), an epithelial-basal lamina-specific LM variant composed of the α3, β3 and γ2 chains. It has been reported that LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, such as colon, pancreas, lung, cervix, stomach, and prostate cancer [ 32 – 34 ]. Currently, multiple regulation models of laminin 332 have been discovered in tumor progression, including transcription and protein stabilization modulation [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis

Zhang

Liu

et al. 2022

J Exp Clin Cancer Res

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Background The development of lethal cancer metastasis depends on the dynamic interactions between cancer cells and the tumor microenvironment, both of which are embedded in the extracellular matrix (ECM). The acquisition of resistance to detachment-induced apoptosis, also known as anoikis, is a critical step in the metastatic cascade. Thus, a more in-depth and systematic analysis is needed to identify the key drivers of anoikis resistance. Methods Genome-wide CRISPR/Cas9 knockout screen was used to identify critical drivers of anoikis resistance using SKOV3 cell line and found protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) as a candidate. Quantitative real-time PCR (qRT-PCR) and immune-histochemistry (IHC) were used to measure differentially expressed PCMT1 in primary tissues and metastatic cancer tissues. PCMT1 knockdown/knockout and overexpression were performed to investigate the functional role of PCMT1 in vitro and in vivo. The expression and regulation of PCMT1 and integrin-FAK-Src pathway were evaluated using immunoprecipitation followed by mass spectrometry (IP-MS), western blot analysis and live cell imaging. Results We found that PCMT1 enhanced cell migration, adhesion, and spheroid formation in vitro. Interestingly, PCMT1 was released from ovarian cancer cells, and interacted with the ECM protein LAMB3, which binds to integrin and activates FAK-Src signaling to promote cancer progression. Strikingly, treatment with an antibody against extracellular PCMT1 effectively reduced ovarian cancer cell invasion and adhesion. Our in vivo results indicated that overexpression of PCMT1 led to increased ascites formation and distant metastasis, whereas knockout of PCMT1 had the opposite effect. Importantly, PCMT1 was highly expressed in late-stage metastatic tumors compared to early-stage primary tumors. Conclusions Through systematically identifying the drivers of anoikis resistance, we uncovered the contribution of PCMT1 to focal adhesion (FA) dynamics as well as cancer metastasis. Our study suggested that PCMT1 has the potential to be a therapeutic target in metastatic ovarian cancer.

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Identification of a Novel Mutation ofLAMB3Gene in a Lybian Patient with Hereditary Epidermolysis Bullosa by Whole Exome Sequencing

Cited by 4 publications

References 9 publications

Successful Multidisciplinary Treatment of Chronic Facial Wounds in Junctional Epidermolysis Bullosa

Successful Multidisciplinary Treatment of Chronic Facial Wounds in Junctional Epidermolysis Bullosa

LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway

Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis

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