SLC7A11 as a biomarker and therapeutic target in HPV-positive head and neck Squamous Cell Carcinoma

Anais Hémon; Christophe Louandre; Claire Lailler; Corinne Godin; Maxime Bottelin; Virginie Morel; Catherine François; Antoine Galmiche; Zuzana Saidak

doi:10.1016/j.bbrc.2020.09.134

SLC7A11 as a biomarker and therapeutic target in HPV-positive head and neck Squamous Cell Carcinoma

Biochem Biophys Res Commun. 2020 Dec 17;533(4):1083-1087. doi: 10.1016/j.bbrc.2020.09.134. Epub 2020 Oct 3.

Authors

Anais Hémon¹, Christophe Louandre¹, Claire Lailler¹, Corinne Godin¹, Maxime Bottelin², Virginie Morel³, Catherine François³, Antoine Galmiche⁴, Zuzana Saidak¹

Affiliations

¹ Equipe CHIMERE, EA7516, Université de Picardie Jules Verne, Amiens, France; Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Amiens, France.
² Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Amiens, France.
³ Laboratoire de Virologie, Centre de Biologie Humaine, CHU Amiens, France.
⁴ Equipe CHIMERE, EA7516, Université de Picardie Jules Verne, Amiens, France; Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Amiens, France. Electronic address: [email protected].

PMID: 33019976
DOI: 10.1016/j.bbrc.2020.09.134

Abstract

Ferroptosis, a regulated form of cell necrosis was previously reported to be induced upon pharmacological targeting of the cystine transporter SLC7A11 in Head and neck Squamous Cell Carcinoma (HNSCC). Whether tumors arising in a context of chronic infection with Human Papillomavirus (HPV) are sensitive to ferroptosis is unknown. Using RNAseq data (both whole-tumor and single-cell sequencing) we report that HPV positive (HPV^+ve) tumors have lower expression levels of SLC7A11 compared to HPV negative (HPV^-ve) HNSCC. We examined in vitro the effect of erastin, a specific blocker of SLC7A11, applied on two HNSCC cell lines with stable expression of HPV16 E6 and E7 oncoproteins. We report a decrease in total GSH levels and an increased sensitivity to erastin-induced ferroptosis in E6-E7 cells. Cell sensitivity to ferroptosis was specificaly related to a defect in cystine transport since we found no difference in ferroptosis induced by the direct inhibition of GPX4, and N-Acetyl Cystein abolished the difference between WT and E6-E7-expressing cells. Our findings point to SLC7A11 as an HPV-related biomarker of potential therapeutic relevance in HNSCC. Targeting cystine import to promote ferroptosis might be a promising strategy against HPV^+ve HNSCC. (188 words).

Keywords: Erastin; Ferroptosis; HNSCC; Human papillomavirus 16; SLC7A11.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / metabolism
Amino Acid Transport System y+ / antagonists & inhibitors
Amino Acid Transport System y+ / genetics
Amino Acid Transport System y+ / metabolism*
Biological Transport, Active / drug effects
Biological Transport, Active / genetics
Biomarkers / metabolism
Cell Line, Tumor
Cystine / metabolism
Ferroptosis / drug effects
Ferroptosis / genetics*
Gene Expression Regulation, Neoplastic / drug effects
Gene Expression Regulation, Neoplastic / genetics
Glutathione / metabolism
Head and Neck Neoplasms / genetics
Head and Neck Neoplasms / metabolism*
Head and Neck Neoplasms / virology*
Human papillomavirus 16 / metabolism*
Humans
Oncogene Proteins, Viral / metabolism
Papillomavirus E7 Proteins / metabolism
Papillomavirus Infections / virology
Phospholipid Hydroperoxide Glutathione Peroxidase / antagonists & inhibitors
Piperazines / pharmacology
RNA-Seq
Repressor Proteins / metabolism
Single-Cell Analysis
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / metabolism*
Squamous Cell Carcinoma of Head and Neck / virology*

Substances

Amino Acid Transport System y+
Biomarkers
E6 protein, Human papillomavirus type 16
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Piperazines
Repressor Proteins
SLC7A11 protein, human
erastin
Cystine
Phospholipid Hydroperoxide Glutathione Peroxidase
Glutathione
Acetylcysteine