Signaling by the Extracellular Matrix Protein Reelin Promotes Granulosa Cell Proliferation in the Chicken Follicle

Eresheim, Christine; Leeb, Christian; Buchegger, Patricia; Nimpf, Johannes

doi:10.1074/jbc.m113.533489

Cited by 32 publications

(27 citation statements)

References 38 publications

(67 reference statements)

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“…The extracellular matrix protein Reelin has been found to promote the proliferation of intestinal and submandibular gland epithelial cells and granulose cells via ApoERs (VLDLR)/Dab1/PI3K/Akt and MAPK pathways303132. Whether similar function and similar signaling pathways can be found in Reelin-expressing tumors are not clear.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix protein Reelin promotes myeloma progression by facilitating tumor cell proliferation and glycolysis

Qin

Lin

Cao

et al. 2017

Sci Rep

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Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells. The activation of FAK/Syk/Akt/mTOR and STAT3 pathways contributes to Reelin-induced cancer cell growth and metabolic reprogramming. Our findings further reveal that activated Akt and STAT3 pathways induce the upregulation of HIF1α and its downstream targets (LDHA and PDK1), leading to increased glycolysis in myeloma cells. Together, our results demonstrate the critical contributions of Reelin to myeloma growth and metabolism. It presents an opportunity for myeloma therapeutic intervention by inhibiting Reelin and its signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Extracellular matrix protein Reelin promotes myeloma progression by facilitating tumor cell proliferation and glycolysis

Qin

Lin

Cao

et al. 2017

Sci Rep

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“…Reelin expression was reported in the bovine endometrium and in the theca layer of the bovine follicle (Fayad et al, ; Cerri et al, ), while the reelin receptor ApoER2 is expressed in the granulosa cell layer (Fayad et al, ). A similar expression pattern is observed in the chicken follicle, where reelin is expressed in the theca layer, and the receptors VLDLR and ApoER2, as well as the adaptor Dab1 are expressed in granulosa cells of the chicken follicle (Eresheim et al, ).…”

Section: Reelin Signaling Activity In Adult Non‐neuronal Tissuesmentioning

confidence: 58%

Nonneuronal roles for the reelin signaling pathway

Khialeeva

Carpenter

2016

Developmental Dynamics

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The reelin signaling pathway has been established as an important regulator of cell migration during development of the central nervous system, and disruptions in reelin signaling alter the positioning of many types of neurons. Reelin is a large extracellular matrix glycoprotein and governs cell migration through activation of multiple intracellular signaling events by means of the receptors ApoE receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR), and the intracellular adaptor protein Disabled-1 (Dab1). Earlier studies reported expression of reelin in nonneuronal tissues, but the functions of this signaling pathway outside of the nervous system have not been studied until recently. A large body of evidence now suggests that reelin functions during development and disease of multiple nonneuronal tissues. This review addresses recent advances in the field of nonneuronal reelin signaling. Developmental Dynamics 246:217-226,

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“…In addition, neither LY294002 nor Rapamycin suppressed FSH-induced PRLR levels but both did potentiate the stimulation of FSH on StAR expression (Fig 6A and 6C). Since both pro-survival and proliferative effects of the PI3K-Akt-mTOR signaling have been demonstrated in chicken or goose granulosa cells [37, 52, 53], it is hypothesized that in hen undifferentiated follicles, suppression of this pathway may depress proliferation and promote steroidogenesis to initiate granulosa cell differentiation. As a cellular energy sensor, AMPK is widely expressed in chicken preovulatory granulosa cells and is involved in FSH- or IGF-regulated steroidogenesis via modulation of several steroidogenic enzymes expression such as StAR and 3βHSD [9, 54].…”

Section: Discussionmentioning

confidence: 99%

Regulatory Mechanisms Underlying the Expression of Prolactin Receptor in Chicken Granulosa Cells

Duggavathi

Zadworny

2017

PLoS ONE

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Prolactin (PRL) has both pro- and anti-gonadal roles in the regulation of avian ovarian functions through its interaction with the receptor (PRLR). However, neither the pattern of expression of PRLR nor its regulatory mechanisms during follicle development have been clearly defined. The objective of the present study was to investigate mechanisms of PRLR expression in chicken granulosa cells. Levels of PRLR transcript were highest in the stroma and walls of follicles < 2 mm in diameter and progressively declined with the maturation of follicles. In preovulatory follicles, PRLR was expressed at higher levels in granulosa than theca layers. FSH exerted the greatest stimulatory effect on PRLR and StAR expression in cultured granulosa cells of the 6–8 mm follicles but this effect declined as follicles matured to F1. In contrast, LH did not alter the expression of PRLR in granulosa cells of all follicular classes but increased levels of StAR in F2 and F1 granulosa cells. Both non-glycosylated- (NG-) and glycosylated- (G-) PRL upregulated basal PRLR expression in granulosa cells of the 6–8 mm, F3 or F1 follicles but had little effect in F2 follicles. Furthermore, FSH-stimulated PRLR expression was reduced by the addition of either isoform of PRL especially in F2 granulosa cells. These results indicate that PRLR is differentially distributed and regulated by FSH or PRL variants independently or in combination in the follicular hierarchy. By using activators and inhibitors, we further demonstrated that multiple signaling pathways, including PKA, PKC, PI3K, mTOR and AMPK, are not only directly involved in, but they can also converge to modulate ERK2 activity to regulate FSH-mediated PRLR and StAR expression in undifferentiated granulosa cells. These data provide new insights into the regulatory mechanisms controlling the expression of PRLR in granulosa cells.

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Signaling by the Extracellular Matrix Protein Reelin Promotes Granulosa Cell Proliferation in the Chicken Follicle

Cited by 32 publications

References 38 publications

Extracellular matrix protein Reelin promotes myeloma progression by facilitating tumor cell proliferation and glycolysis

Extracellular matrix protein Reelin promotes myeloma progression by facilitating tumor cell proliferation and glycolysis

Nonneuronal roles for the reelin signaling pathway

Regulatory Mechanisms Underlying the Expression of Prolactin Receptor in Chicken Granulosa Cells

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