Open AccessmiR‐9 modulates and predicts the response to radiotherapy and EGFR inhibition in HNSCC
Author(s) -
Citron Francesca,
Segatto Ilenia,
Musco Lorena,
Pellarin Ilenia,
Rampioni Vinciguerra Gian Luca,
Franchin Giovanni,
Fanetti Giuseppe,
Miccichè Francesco,
Giacomarra Vittorio,
Lupato Valentina,
Favero Andrea,
Concina Isabella,
Srinivasan Sanjana,
Avanzo Michele,
Castiglioni Isabella,
Barzan Luigi,
Sulfaro Sandro,
Petrone Gianluigi,
Viale Andrea,
Draetta Giulio F,
Vecchione Andrea,
Belletti Barbara,
Baldassarre Gustavo
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202012872
Subject(s) - cetuximab , head and neck squamous cell carcinoma , cancer research , radiation therapy , egfr inhibitors , epidermal growth factor receptor , medicine , biomarker , in vivo , cisplatin , oncology , transcription factor , head and neck cancer , biology , cancer , chemotherapy , gene , colorectal cancer , biochemistry , microbiology and biotechnology
Radiotherapy (RT) plus the anti‐EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR‐9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT‐induced cell death. Mechanistically, by targeting KLF5, miR‐9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo . Intriguingly, high miR‐9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR‐9 expression correlated with Sp1 mRNA levels and high miR‐9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR‐9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy.