scholarly journals PICK1 Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance

PLoS Biology ◽  
2013 ◽  
Vol 11 (4) ◽  
pp. e1001542 ◽  
Author(s):  
Birgitte Holst ◽  
Kenneth L. Madsen ◽  
Anna M. Jansen ◽  
Chunyu Jin ◽  
Mattias Rickhag ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Growth Retardation ◽  
Secretory Vesicle ◽  
Vesicle Biogenesis

scholarly journals PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma

2020 ◽  
Vol 12 (527) ◽  
pp. eaax3772 ◽  
Author(s):  
Xiaochao Tan ◽  
Priyam Banerjee ◽  
Edward A. Pham ◽  
Florentine U. N. Rutaganira ◽  
Kaustabh Basu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Survival ◽  
Cancer Cell ◽  
Secretory Vesicle ◽  
Effector Proteins ◽  
Therapeutic Implications ◽  
Chromosome 1Q ◽  
Biological Studies ◽  
Cancer Cell Survival ◽  
Vesicle Biogenesis

Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)–dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

scholarly journals Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3–amplified lung adenocarcinoma cells

2021 ◽  
Vol 118 (25) ◽  
pp. e2023537118
Author(s):  
Lei Shi ◽  
Xiaochao Tan ◽  
Xin Liu ◽  
Jiang Yu ◽  
Neus Bota-Rabassedas ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Protein Secretion ◽  
Secretory Vesicle ◽  
Effector Protein ◽  
Alternative Source ◽  
Adenocarcinoma Cells ◽  
Vesicle Biogenesis ◽  
Competing Endogenous Rna Network ◽  
Cancer Types

A chromosome 1q21.3 region that is frequently amplified in diverse cancer types encodes phosphatidylinositol (PI)-4 kinase IIIβ (PI4KIIIβ), a key regulator of secretory vesicle biogenesis and trafficking. Chromosome 1q21.3–amplified lung adenocarcinoma (1q-LUAD) cells rely on PI4KIIIβ for Golgi-resident PI-4-phosphate (PI4P) synthesis, prosurvival effector protein secretion, and cell viability. Here, we show that 1q-LUAD cells subjected to prolonged PI4KIIIβ antagonist treatment acquire tolerance by activating an miR-218-5p–dependent competing endogenous RNA network that up-regulates PI4KIIα, which provides an alternative source of Golgi-resident PI4P that maintains prosurvival effector protein secretion and cell viability. These findings demonstrate an addiction to Golgi-resident PI4P synthesis in a genetically defined subset of cancers.

scholarly journals Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A

2008 ◽  
Vol 181 (7) ◽  
pp. 5024-5034 ◽  
Author(s):  
Prerna Prasad ◽  
Angel A. Yanagihara ◽  
Andrea L. Small-Howard ◽  
Helen Turner ◽  
Alexander J. Stokes
Keyword(s):  
Mast Cells ◽  
Chromogranin A ◽  
Secretory Vesicle ◽  
Vesicle Biogenesis

scholarly journals Relationship between growth retardation and impaired glucose tolerance in hypothyroidal growth-retarded (grt) mice

2010 ◽  
Vol 50 (3) ◽  
pp. 186-192 ◽  
Author(s):  
Yoshie Tasaki ◽  
Yusuke Taguchi ◽  
Takeo Machida ◽  
Tetsuya Kobayashi
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Growth Retardation

Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance

2015 ◽  
Vol 28 (1-2) ◽  
Author(s):  
Sebastian Burkhardt ◽  
Julia Gesing ◽  
Thomas M. Kapellen ◽  
Peter Kovacs ◽  
Jürgen Kratzsch ◽  
...  
Keyword(s):  
Growth Factor ◽  
Genetic Analysis ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Gestational Age ◽  
Growth Retardation ◽  
Small For Gestational Age ◽  
Heterozygous Mutation ◽  
Genetic Condition ◽  
Metabolic Complications

AbstractInfants born small for gestational age (SGA) are at risk to develop metabolic complications. Insulin-like growth factor 1 (IGF-1) resistance due to IGF-1 receptor (IGF1R) mutations is a rare genetic condition that causes proportionate growth retardation. The contribution of an impaired IGF1R function to the development of comorbidities such as disturbed glucose homeostasis is not well understood. Genetic analysis and detailed auxological, endocrine and psychological investigations in two male SGA siblings were performed. The two patients and their father bear a novel heterozygous mutation (p.Cys1248Tyr) in the

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