Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation

Abstract

In patients with obstructive sleep apnea (OSA), intermittent hypoxia (IH) induces overexpression of paraspeckle component 1 (PSPC1), a master modulator of transforming growth factor β (TGF-β) signaling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of IH-induced effect on PSPC1, and its consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma (CM) with or without OSA, and their relationship with tumor aggressiveness along with thein vitroeffects of soluble PSPC1 and IH on melanoma cell aggressiveness mechanisms were assessed.In 292 CM patients, sleep studies and serum levels of PSPC1 and TGFβ were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and IH conditions.PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several CM clinical aggressiveness indicators. Both IH exposures and serum from OSA patients up-regulated TGFβ expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics.In CM patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with IH would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea

“…In agreement, NLRP3 activation in OSA patients has been shown to induce the release of the coagulation initiator tissue factor (TF), that promotes systemic coagulation, thrombosis, and atherosclerosis progression [13,14]. These findings suggest a role of the NLRP3-pyroptosis axis in the release of TF into plasma [15], which could also be involved in the release to the plasma of other intracellular mediators.…”

“…On the other hand, the TGF-β pathway could also limit atherosclerosis progression by modulating the inflammatory response and preventing lipid accumulation in the vessel wall [22]. Interestingly, OSA patients frequently present an increase in TGF-β levels [15,23,24] suggesting that the pathways dependent on its activation could play a role in the high rates of atherosclerotic patients among OSA subjects.…”

Asociación de apnea obstructiva del sueño y cáncer. Un nuevo modelo para el enfoque de la comorbilidad

“…Este fenómeno también resulta relevante en enfermos con un cáncer ya establecido. De hecho, en pacientes con melanoma, la gravedad de la AOS se asocia con mayores niveles séricos de PSPC1, lo cual, junto con la hipoxia intermitente, aumenta las capacidades de autorreprogramación de la transición epitelio-mesénquima y la adquisición de características de CSC por parte de las células del melanoma, promoviendo su agresividad intrínseca 15 .…”

Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer

“…Furthermore, a hypoxia-dependent increase in serum levels of midkine (MDK), a recognised pro-angiogenic and pro-lymphangiogenic factor associated with increased tumour aggressiveness, has been reported in patients with OSA and melanoma [ 18 ]. Finally, OSA is also associated with melanoma aggressiveness through hypoxia-mediated overexpression of paraspeckle component-1 (PSPC1) [ 21 ]. PSPC1 functions as a master activator of metastatic reprogramming by mediating pro-metastatic autocrine signalling of transforming growth factor-β1 (TGF-β1)/SMAD2/3, inducing EMT and acquisition of CSC characteristics [ 22 ].…”