TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance

  • Cancers (Basel). 2020 Nov 5;12(11):3269. doi: 10.3390/cancers12113269.
Yoelsis Garcia-Mayea  1  2 ,  Cristina Mir  1 ,  Laia Carballo  1 ,  Josep Castellvi  1 ,  Jordi Temprana-Salvador  1 ,  Juan Lorente  3 ,  Sergi Benavente  4 ,  Juana M García-Pedrero  5 ,  Eva Allonca  5 ,  Juan P Rodrigo  5 ,  Matilde E LLeonart  1  6
Affiliations
  • 1. Biomedical Research in Cancer Stem Cells, Vall d'Hebron Research Institute (VHIR), Autonomous University of Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
  • 2. Genetic, Microbiology and Statistics Department, Faculty of Biology, University of Barcelona, Avenida Diagonal 643, 08014 Barcelona, Spain.
  • 3. Otorhinolaryngology Department, Hospital Vall d'Hebron (HUVH), Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
  • 4. Radiotherapy Unit, Vall d'Hebron Research Institute (VHIR), Autonomous University of Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
  • 5. Department of Otolaryngology-Head and Neck Surgery, Central University Hospital of Asturias, University of Oviedo, ISPA, IUOPA, Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Av. Roma SN, 33011 Oviedo, Spain.
  • 6. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Vall d'Hebron Research Institute (VHIR), Passeig Vall d´Hebron 119-129, 08035 Barcelona, Spain.
PMID: 33167355 DOI: 10.3390/cancers12113269
Abstract

Sensitization of resistant cells and Cancer Stem Cells (CSCs) represents a major challenge in Cancer therapy. A proteomic study revealed tetraspanin-1 (TSPAN1) as a protein involved in acquisition of cisplatin (CDDP) resistance (Data are available via ProteomeXchange with identifier PXD020159). TSPAN1 was found to increase in CDDP-resistant cells, CSCs and biopsies from head and neck Squamous Cell Carcinoma (HNSCC) patients. TSPAN1 depletion in parental and CDDP-resistant HNSCC cells reduced cell proliferation, induced Apoptosis, decreased Autophagy, sensitized to chemotherapeutic agents and inhibited several signaling cascades, with phospho-SRC inhibition being a major common target. Moreover, TSPAN1 depletion in vivo decreased the size and proliferation of parental and CDDP-resistant Tumors and reduced metastatic spreading. Notably, CDDP-resistant Tumors showed epithelial-mesenchymal transition (EMT) features that disappeared upon TSPAN1 inhibition, suggesting a link of TSPAN1 with EMT and metastasis. Immunohistochemical analysis of HNSCC specimens further revealed that TSPAN1 expression was correlated with phospho-SRC (pSRC), and inversely with E-cadherin, thus reinforcing TSPAN1 association with EMT. Overall, TSPAN1 emerges as a novel oncogenic protein and a promising target for HNSCC therapy.

Keywords
HNSCC; apoptosis; autophagy; cancer; cancer stem cells; resistance.
Products