Radiological findings in Birt–Hogg–Dubé syndrome: a rare differential for pulmonary cysts and renal tumors

Gupta, Pramod Kumar; Eshaghi, Nahid; Kamba, Thompson T.; Ghole, Vidisha; Garcia-Morales, Francisco

doi:10.1016/j.clinimag.2006.09.023

Cited by 16 publications

(7 citation statements)

References 7 publications

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“…Renal cysts were also reported in the literature in some patients aged 40 years and older (7)(8)(9)(10)(11). Six of 13 members of this family, screened by MRI, had multiple renal cysts.…”

Section: Clinical Spectrum and Diagnostic Criteriasupporting

confidence: 67%

Early onset of renal cancer in a family with Birt–Hogg–Dubé syndrome

Kluijt

Jong²,

Teertstra

et al. 2009

Clinical Genetics

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Birt-Hogg-Dubé syndrome is a hereditary syndrome characterized by benign disease of skin and lungs and a risk of malignant renal tumors. We describe a clinical and genetic study of a large Dutch family with a novel mutation in the FLCN gene. Renal cancer at very young age occurred in one branch of this family, while in other branches, cutaneous and pulmonary symptoms predominated. A variety of congenital anomalies and connective tissue abnormalities were observed, possibly associated with the gene mutation.

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“…Renal cysts were also reported in the literature in some patients aged 40 years and older (7)(8)(9)(10)(11). Six of 13 members of this family, screened by MRI, had multiple renal cysts.…”

Section: Clinical Spectrum and Diagnostic Criteriasupporting

confidence: 67%

Early onset of renal cancer in a family with Birt–Hogg–Dubé syndrome

Kluijt

Jong²,

Teertstra

et al. 2009

Clinical Genetics

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“…However, later studies showed a predisposition for all subtypes of kidney cancer including clear cell and papillary subtypes [4]. In addition, BHD confers an increased risk of pulmonary cysts, spontaneous pneumothorax, and cysts of the kidney, pancreas, and liver [3], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Folliculin Regulates Ampk-Dependent Autophagy and Metabolic Stress Survival

et al. 2014

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Dysregulation of AMPK signaling has been implicated in many human diseases, which emphasizes the importance of characterizing AMPK regulators. The tumor suppressor FLCN, responsible for the Birt-Hogg Dubé renal neoplasia syndrome (BHD), is an AMPK-binding partner but the genetic and functional links between FLCN and AMPK have not been established. Strikingly, the majority of naturally occurring FLCN mutations predisposing to BHD are predicted to produce truncated proteins unable to bind AMPK, pointing to the critical role of this interaction in the tumor suppression mechanism. Here, we demonstrate that FLCN is an evolutionarily conserved negative regulator of AMPK. Using Caenorhabditis elegans and mammalian cells, we show that loss of FLCN results in constitutive activation of AMPK which induces autophagy, inhibits apoptosis, improves cellular bioenergetics, and confers resistance to energy-depleting stresses including oxidative stress, heat, anoxia, and serum deprivation. We further show that AMPK activation conferred by FLCN loss is independent of the cellular energy state suggesting that FLCN controls the AMPK energy sensing ability. Together, our data suggest that FLCN is an evolutionarily conserved regulator of AMPK signaling that may act as a tumor suppressor by negatively regulating AMPK function.

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“…57 The AMPK-dependent regulation of hyperosmotic stress that we observed in C. elegans is a very interesting aspect in regards to BHD disease, which is mostly manifested by enlarged renal cysts and tumors in all mammalian models including rats, mice, dogs, and men. [40][41][42]44,48 Since the kidney is an organ chronically exposed to hyperosmotic stress, it is possible that the BHD renal tumors and cysts are formed because of an increased resistance to hyperosmotic conditions, which could lead to DNA damage. In support of this, loss of FLCN and VHL, which are both renal tumor suppressor genes, predispose to renal clear cell carcinomas which are glycogen-rich tumors.…”

Section: The Paradoxical Role Of Ampk In Glycogen Metabolismmentioning

confidence: 99%

“…[38][39][40][41][42][43][44][45][46][47][48][49][50][51] BHD is caused by germline mutations in the BHD gene, which encodes FLCN, a 64KDa protein, expressed in most tissues. 52 Since the discovery of the FLCN gene, diverse FLCN-related cellular functions have been reported.…”

Section: The Paradoxical Role Of Ampk In Glycogen Metabolismmentioning

confidence: 99%

Glycogen: A must have storage to survive stressful emergencies

Possik

Pause

2016

Worm

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Mechanisms of adaptation to acute changes in osmolarity are fundamental for life. When exposed to hyperosmotic stress, cells and organisms utilize conserved strategies to prevent water loss and maintain cellular integrity and viability. The production of glycerol is a common strategy utilized by the nematode Caenorhabditis elegans (C. elegans) and many other organisms to survive hyperosmotic stress. Specifically, the transcriptional upregulation of glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme in the production of glycerol, has been previously implicated in many model organisms. However, what fuels this massive and rapid production of glycerol upon hyperosmotic stress has not been clearly elucidated. We have recently discovered an AMPK-dependent pathway that mediates hyperosmotic stress resistance in C. elegans. Specifically, we demonstrated that the chronic activation of AMPK leads to glycogen accumulation, which under hyperosmotic stress exposure, is rapidly degraded to mediate glycerol production. Importantly, we demonstrate that this strategy is utilized by flcn-1 mutant C. elegans nematodes in an AMPKdependent manner. FLCN-1 is the worm homolog of the human renal tumor suppressor Folliculin (FLCN) responsible for the Birt-Hogg-Dub e neoplastic syndrome. Here, we comment on the dual role for glycogen in stress resistance: it serves as an energy store and a fuel for osmolyte production. We further discuss the potential utilization of this mechanism by organisms in general and by human cancer cells in order to survive harsh environmental conditions and notably hyperosmotic stress.

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Radiological findings in Birt–Hogg–Dubé syndrome: a rare differential for pulmonary cysts and renal tumors

Cited by 16 publications

References 7 publications

Early onset of renal cancer in a family with Birt–Hogg–Dubé syndrome

Early onset of renal cancer in a family with Birt–Hogg–Dubé syndrome

Folliculin Regulates Ampk-Dependent Autophagy and Metabolic Stress Survival

Glycogen: A must have storage to survive stressful emergencies

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