Tumor metastases are responsible for as much as 90% of all cancer-related deaths, yet it remains the most poorly understood feature of cancer pathogenesis. Malignant cell transformation and invasion of distant tissues requires metabolic reprogramming to support anabolic cell growth and cancer cell survival under hypoxic conditions. Our lab focuses on the study of the pathogenic mechanisms of metastasis that can be used for the development of new therapeutic opportunities. Our approaches include the analysis of metastatic cell phenotypes such as cell migration, cell-to-cell communication and collective cell invasion by focussing in the understandings of the intersection between hypoxia and metabolism. Relevant findings obtained in cell-based systems are validated in human tumor tissues derived from metastatic head and neck squamous cell carcinomas and paragangliomas/pheochromocytomas. We have disclosed relevant roles of hypoxia on the cell-to-cell trafficking of mitochondria and on the activation of signalling pathways that impact on mitochondrial activity and promotes poor prognosis in cancer patients. On another hand, metabolic dysfunction by mutations in the succinate dehydrogenase B mitochondrial complex II subunit also impact on metastasis development through the epigenetic repression of cell differentiation programs.
Bernardo-Castiñeira C, Valdés N, Sierra MI, Sáenz-de-Santa-María I, Bayón GF, Perez RF, Fernández AF, Fraga MF, Astudillo A, Menéndez R, Fernández B, Del Olmo M, Suarez C, Chiara MD. SDHC Promoter Methylation, a Novel Pathogenic Mechanism in Parasympathetic Paragangliomas. J Clin Endocrinol Metab. 2018 Jan 1;103(1):295-305.
Sáenz-de-Santa-María I, Bernardo-Castiñeira C, Enciso E, García-Moreno I, Chiara JL, Suarez C, Chiara MD. Control of long-distance cell-to-cell communication and autophagosome transfer in squamous cell carcinoma via tunneling nanotubes. Oncotarget. 2017 Mar 28;8(13):20939-20960.
Sáenz-de-Santa-María I, Bernardo-Castiñeira C, Secades P, Bernaldo-de-Quirós S, Rodrigo JP, Astudillo A, Chiara MD. Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation. Oncotarget. 2017 Feb 21;8(8):13730-13746.
Merlo A, Bernardo-Castiñeira C, Sáenz-de-Santa-María I, Pitiot AS, Balbín M, Astudillo A, Valdés N, Scola B, Del Toro R, Méndez-Ferrer S, Piruat JI, Suarez C, Chiara MD. Role of VHL, HIF1A and SDH on the expression of miR-210: Implications for tumoral pseudo-hypoxic fate. Oncotarget. 2017 Jan 24;8(4):6700-6717.
Merlo A, de Quirós SB, de Santa-María IS, Pitiot AS, Balbín M, Astudillo A, Scola B, Arístegui M, Quer M, Suarez C, Chiara MD. Identification of somatic VHL gene mutations in sporadic head and neck paragangliomas in association with activation of the HIF-1α/miR-210 signaling pathway. J Clin Endocrinol Metab. 2013 Oct;98(10):E1661-6.