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

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.

Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells

“…EMT, characterized by the loss of cell-cell adhesion as well as the initiation of invasion and metastasis, plays a critical role in resistance to most conventional therapeutics (Gaponova et al, 2020;Garcia-Mayea et al, 2020). The hallmarks of EMT are loss of E-cadherin expression, gain of mesenchymal markers, and increased mortality.…”

JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

“…So far, cisplatin-based treatment is still the standard regimen for HNSCC patients. However, intrinsic and acquired resistance to cisplatin is a major challenge to achieve a long-term curative effect and results in early recurrence and metastasis [ 33 – 35 ]. Therefore, there is an urgent need to find efficient means to improve cisplatin sensitivity.…”

SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation

“…Primary tumors from patients with larynx squamous cell carcinoma were collected from Vall d’Hebron University Hospital (HUVH) for cell culture and protein analysis. The establishment of a primary cell culture from these laryngeal biopsies was performed as previously described [ 13 , 14 ]. The study was performed according to the Declaration of Helsinki and approved by the Ethics Committee of Vall d’Hebron Hospital (CEIC) (Ref.…”

“…All the cell lines were cultured in MEM (Gibco, Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS) (Biowest, Nuaillé-France), 1% penicillin-streptomycin (Pen 20 U/mL and Strep 20 μg/mL, Gibco, Thermo Fisher, Waltham, MA, USA). Resistant cell lines and CSCs were generated as described [ 14 ].…”