SOX2 as a novel contributor of oxidative metabolism in melanoma cells

Elena Andreucci†,
Silvia Pietrobono†,
Silvia Peppicelli,
Jessica Ruzzolini,
Francesca Bianchini,
Alessio Biagioni,
Barbara Stecca and
Lido CaloriniEmail author View ORCID ID profile

†Contributed equally

Cell Communication and Signaling201816:87

https://doi.org/10.1186/s12964-018-0297-z

Received: 19 July 2018
Accepted: 8 November 2018
Published: 22 November 2018

Abstract

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 HIF1α pathway disruption.