PMID- 30466459
OWN - NLM
STAT- MEDLINE
DCOM- 20190515
LR  - 20190515
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 16
IP  - 1
DP  - 2018 Nov 22
TI  - SOX2 as a novel contributor of oxidative metabolism in melanoma cells.
PG  - 87
LID - 10.1186/s12964-018-0297-z [doi]
LID - 87
AB  - BACKGROUND: Deregulated metabolism is a hallmark of cancer and recent evidence 
      underlines that targeting tumor energetics may improve therapy response and 
      patient outcome. Despite the general attitude of cancer cells to exploit the 
      glycolytic pathway even in the presence of oxygen (aerobic glycolysis or "Warburg 
      effect"), tumor metabolism is extremely plastic, and such ability to switch from 
      glycolysis to oxidative phosphorylation (OxPhos) allows cancer cells to survive 
      under hostile microenvironments. Recently, OxPhos has been related with malignant 
      progression, chemo-resistance and metastasis. OxPhos is induced under 
      extracellular acidosis, a well-known characteristic of most solid tumors, 
      included melanoma. METHODS: To evaluate whether SOX2 modulation is correlated 
      with metabolic changes under standard or acidic conditions, SOX2 was silenced and 
      overexpressed in several melanoma cell lines. To demonstrate that SOX2 directly 
      represses HIF1A expression we used chromatin immunoprecipitation (ChIP) and 
      luciferase assay. RESULTS: In A375-M6 melanoma cells, extracellular acidosis 
      increases SOX2 expression, that sustains the oxidative cancer metabolism 
      exploited under acidic conditions. By studying non-acidic SSM2c and 501-Mel 
      melanoma cells (high- and very low-SOX2 expressing cells, respectively), we 
      confirmed the metabolic role of SOX2, attributing SOX2-driven OxPhos 
      reprogramming to HIF1alpha pathway disruption. CONCLUSIONS: SOX2 contributes to the 
      acquisition of an aggressive oxidative tumor phenotype, endowed with enhanced 
      drug resistance and metastatic ability.
FAU - Andreucci, Elena
AU  - Andreucci E
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy.
FAU - Pietrobono, Silvia
AU  - Pietrobono S
AD  - Core Research Laboratory, Institute for Cancer Research and Prevention (ISPRO), 
      Florence, Italy.
FAU - Peppicelli, Silvia
AU  - Peppicelli S
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy.
FAU - Ruzzolini, Jessica
AU  - Ruzzolini J
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy.
FAU - Bianchini, Francesca
AU  - Bianchini F
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy.
FAU - Biagioni, Alessio
AU  - Biagioni A
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy.
FAU - Stecca, Barbara
AU  - Stecca B
AD  - Core Research Laboratory, Institute for Cancer Research and Prevention (ISPRO), 
      Florence, Italy.
FAU - Calorini, Lido
AU  - Calorini L
AUID- ORCID: 0000-0002-5508-4200
AD  - Department of Clinical and Experimental Biomedical Sciences "Mario Serio", 
      Section of Experimental Pathology and Oncology, University of Florence, Viale 
      G.B. Morgagni, 50, 50134, Florence, Italy. lido.calorini@unifi.it.
AD  - Center of Excellence for Research, Transfer and High Education DenoTHE University 
      of Florence, Florence, Italy. lido.calorini@unifi.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
SB  - IM
MH  - Cell Line, Tumor
MH  - Extracellular Space/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Melanoma/*pathology
MH  - Oxidation-Reduction
MH  - Oxidative Phosphorylation
MH  - Phenotype
MH  - SOXB1 Transcription Factors/genetics/*metabolism
PMC - PMC6249961
OTO - NOTNLM
OT  - HIF1alpha
OT  - Melanoma
OT  - Oxidative metabolism
OT  - SOX2
OT  - Tumor extracellular acidosis
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2018/11/24 06:00
MHDA- 2019/05/16 06:00
PMCR- 2018/11/22
CRDT- 2018/11/24 06:00
PHST- 2018/07/19 00:00 [received]
PHST- 2018/11/08 00:00 [accepted]
PHST- 2018/11/24 06:00 [entrez]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2019/05/16 06:00 [medline]
PHST- 2018/11/22 00:00 [pmc-release]
AID - 10.1186/s12964-018-0297-z [pii]
AID - 297 [pii]
AID - 10.1186/s12964-018-0297-z [doi]
PST - epublish
SO  - Cell Commun Signal. 2018 Nov 22;16(1):87. doi: 10.1186/s12964-018-0297-z.