Apolipoprotein M inhibits proliferation and migration of larynx carcinoma cells

Xue, Haixiang; Yu, Miaomei; Zhou, Ying; Zhang, Jun; Mu, Qinfeng; Chen, Tongbing; Luo, Guanghua; Liu, Jisheng

doi:10.1038/s41598-020-76480-w

Cited by 10 publications

(5 citation statements)

References 21 publications

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“…33 Apolipoprotein M (APOM) can suppress the proliferation and invasion of hepatocellular carcinoma, 34 breast cancer 35, and larynx carcinoma. 36 These coincided with up-regulated S100P and AFAP1-AS1 and down-regulation of APOM in RNA-seq data of LSD PTV carrier organoids.…”

Section: Discussionmentioning

confidence: 52%

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Park

Koh

Kim

et al. 2023

Preprint

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Lysosome is closely linked to autophagy, which plays a vital role in pancreatic adenocarcinoma (PDAC) tumor biology. This study investigated whether lysosome storage dysfuncton(LSD) contributes to PDAC development. Germline putative pathogenic variants (PPVs) in genes involved in lysosome functions were compared between PDAC patients (N=418) and healthy controls (N=845). Furthermore, Galc-knockout mouse pancreas organoids and human PDAC organoids were used to evaluate the consequences of PPV status in PDAC development and establishment. LSD PPVs were enriched in PDAC patients (Log2OR=1.65, P=3.08×10−3). PPV carriers diagnosed with PDAC were younger than non-carriers (61.5 vs. 65.3 years, P=0.031). Hampered autophagolysosome activity with increased autophagy flux and elevated Ki-67 index were observed following GALC downregulation. RNA sequencing of human PDAC organoids revealed upregulation of metabolism related to LSD. Genetically defined lysosome dysfunction is frequently observed in young-age onset PDACs. Lysosome dysfunction might contribute to PDAC development via altered metabolism and impaired autophagolysosome activity.

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Section: Discussionmentioning

confidence: 52%

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Park

Koh

Kim

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 52%

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Koh

Kim

Song

et al. 2023

Preprint

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Lysosome is closely linked to autophagy, which plays a vital role in pancreatic adenocarcinoma (PDAC) tumor biology. This study investigated whether lysosome storage dysfunction (LSD) contributes to PDAC development. Germline putative pathogenic variants (PPVs) in genes involved in lysosome functions were compared between PDAC patients (N=418) and healthy controls (N=845). Furthermore, Galc-knockout mouse pancreas organoids and human PDAC organoids were used to evaluate the consequences of PPV status in PDAC development and establishment. LSD PPVs were enriched in PDAC patients (Log2OR=1.65). PPV carriers diagnosed with PDAC were younger than non-carriers (61.5 vs. 65.3 years, P=0.031). Hampered autophagolysosome activity with increased autophagy flux and elevated Ki-67 index were observed following GALC downregulation. RNA sequencing of human PDAC organoids revealed upregulation of metabolism related to LSD. Genetically defined lysosome dysfunction is frequently observed in young-age onset PDACs. Lysosome dysfunction might contribute to PDAC development via altered metabolism and impaired autophagolysosome activity.

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“…Knockdown of AFAP1-AS1 attenuated PDAC cell proliferation, migration, and invasion [ 66 ]. Apolipoprotein M (APOM) can suppress the proliferation and invasion of hepatocellular carcinoma [ 67 ], breast cancer [ 68 ], and larynx carcinoma [ 69 ]. These results are in agreement with upregulation of S100P and AFAP1-AS1 and downregulation of APOM in the RNA-seq data of PDOs carrying LSD PPVs.…”

Section: Discussionmentioning

confidence: 99%

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma

Koh,

Kim,

Joo

et al. 2023

J Transl Med

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Background Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. Methods The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. Results The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10–3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. Conclusions Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.

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Apolipoprotein M inhibits proliferation and migration of larynx carcinoma cells

Cited by 10 publications

References 21 publications

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Lysosomal Storage Dysfunction, a Germline Variants Affecting Pancreatic Ductal Adenocarcinoma Development and Progression

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma

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