Troy binding to lymphotoxin-α activates NF&amp;kappa;B mediated transcription

Hashimoto, Tsuyoshi; Schlessinger, David; Cui, Chang‐Yi

doi:10.4161/cc.7.1.5135

Cited by 25 publications

(25 citation statements)

References 33 publications

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“…One of the genes that closely followed the expression pattern of Lgr5 in intestinal crypts was Troy (encoded by Tnfrsf19 ). Troy potentially functions as a receptor for lymphotoxin A (Hashimoto et al, 2008). It is highly homologous to two other Tnfrsf members, Xedar and Edar .…”

Section: Resultsmentioning

confidence: 99%

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Stange

Koo

Huch

et al. 2013

Cell

457

473

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SUMMARY Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bi-directionally towards pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing using a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent ‘reserve’ stem cells. These observations challenge the notion that stem cell hierarchies represent a 'one-way street'.

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Section: Resultsmentioning

confidence: 99%

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Stange

Koo

Huch

et al. 2013

Cell

457

473

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“…It has been reported that lymphotoxin-α is a ligand for TROY and that lymphotoxin-α binding to TROY activated NF-κB reporter activity (40) although the biological significance of this interaction is unknown. The cytoplasmic domain of TROY contains a conserved protein module designated the membrane proximal domain.…”

Section: Discussionmentioning

confidence: 99%

TROY (TNFRSF19) Promotes Glioblastoma Survival Signaling and Therapeutic Resistance

Loftus

Dhruv

Tuncali

et al. 2013

Molecular Cancer Research

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Of the features that characterize glioblastoma, arguably none is more clinically significant than the propensity of malignant glioma cells to aggressively invade into the surrounding normal brain tissue. These invasive cells render complete resection impossible, confer significant resistance to chemo- and radiation-therapy, and virtually assure tumor recurrence. Expression of TROY (TNFRSF19), a member of the tumor necrosis factor receptor superfamily, inversely correlates with patient survival and stimulates glioblastoma cell migration and invasion in vitro. In this study, we report that TROY is overexpressed in glioblastoma tumor specimens and TROY mRNA expression is increased in the invasive cell population in vivo. In addition, inappropriate expression of TROY in mouse astrocytes in vivo using glial-specific gene transfer in transgenic mice induces astrocyte migration within the brain validating the importance of the TROY signaling cascade in glioblastoma cell migration and invasion. Moreover, knockdown of TROY expression in a primary glioblastoma xenograft significantly prolonged survival in vivo. We also report that TROY expression significantly increases resistance of glioblastoma cells to both IR- and TMZ- induced apoptosis in vitro via activation of Akt and NF-κB. Inhibition of either Akt or NF-κB activity suppressed the survival benefits of TROY signaling in response to TMZ treatment. These findings position aberrant expression and/or signaling by TROY as a contributor to the dispersion of glioblastoma cells and therapeutic resistance.

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“…However, embryonic generation of thymic medullary epithelial cells depends on RANKL, yet CD40L can partially compensate after birth (5), suggesting that, if RANK is active in the developing skin, it may be masked by other TNF receptor family members such as Edar or Troy (41)(42)(43). Interestingly, lymphotoxin-α-which, like RANKL, functions in lymphoid organ development-also plays a role in HF morphogenesis (44) and is a ligand for Troy (45).…”

Section: Discussionmentioning

confidence: 99%

Receptor activator of NF-κB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit

Duhéron

Hess

Duval

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Receptor activator of NF-κB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermopilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities.R eceptor activator of NF-κB (RANK), a member of the TNF receptor family (TNFRSF11a), was originally identified as a regulator of bone density. Mice deficient in Rank or Rankl display increased bone density owing to reduced osteoclast formation, but the loss of the RANK ligand (RANKL) decoy receptor osteoprotegerin (OPG) results in lower bone mass because of unchecked RANK activation (1, 2).RANK has emerged as an important player in epithelial cell growth and differentiation. It is required for the formation of lactating mammary glands (3, 4), thymic medullary epithelial cells (5), and intestinal microfold cells (6) and has been implicated in the growth and metastasis of prostate (7) and mammary epithelial cancers (8, 9). Thus, RANK affects a great variety of epithelial cells of different organs. The skin is the largest epithelial surface, and its epidermo-pilosebaceous unit comprises the interfollicular epidermis (IFE), the hair follicle (HF), and the sebaceous gland. The HF has the particularity of undergoing cycles of growth (anagen), regression (catagen), and relative quiescence (telogen) (10), making it an excellent system for studying epidermal (stem) cells and organ remodeling (11)(12)(13)(14). Each HF is composed of a permanent upper portion, which includes the sebaceous gland and the bulge region, and a temporary lower cycling portion. The local balance of hair growth stimulators and inhibitors is critical for initiation of new hair growth (15-17). Intriguingly, many of these molecular players also operate in bone development and remodeling (e.g., members of the TGF-β superfamily and their antagonists, parathyroid hormo...

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Troy binding to lymphotoxin-α activates NFκB mediated transcription

Cited by 25 publications

References 33 publications

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

TROY (TNFRSF19) Promotes Glioblastoma Survival Signaling and Therapeutic Resistance

Receptor activator of NF-κB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit

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