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

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Abstract

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Therapy resistance in head and neck squamous cell carcinoma (HNSCC) patients is the main obstacle to achieve more effective treatments that improve survival and quality of life of these patients. Therefore, it is of vital importance to unravel the molecular and cellular mechanisms by which tumor cells acquire resistance to chemotherapy. We conducted a comparative proteomic study involving cisplatin-resistant cells and cancer stem cells with the aim of identifying proteins potentially implicated in the acquisition of cisplatin resistance. Through this study, we identified for the first time tetraspanin-1 (TSPAN1) as an important protein involved in the development, progression and chemoresistance of HNSCC tumors.

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.

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Most cited references 56

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Cancer statistics, 2019

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

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The PRIDE database and related tools and resources in 2019: improving support for quantification data

Yasset Perez-Riverol, Attila Csordas, Jingwen Bai … (2018)

Abstract The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world’s largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3 years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas.

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UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

Darshan S. Chandrashekar, Bhuwan Bashel, Sai Balasubramanya … (2017)

Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. The large sample numbers in TCGA offer an excellent opportunity to address questions associated with tumo heterogeneity. Exploration of the data by cancer researchers and clinicians is imperative to unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed to aid researchers in carrying out specific TCGA data analyses; however there is need for resources to facilitate the study of gene expression variations and survival associations across tumors. Here, we report UALCAN, an easy to use, interactive web-portal to perform to in-depth analyses of TCGA gene expression data. UALCAN uses TCGA level 3 RNA-seq and clinical data from 31 cancer types. The portal's user-friendly features allow to perform: 1) analyze relative expression of a query gene(s) across tumor and normal samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinicopathologic features, 2) estimate the effect of gene expression level and clinicopathologic features on patient survival; and 3) identify the top over- and under-expressed (up and down-regulated) genes in individual cancer types. This resource serves as a platform for in silico validation of target genes and for identifying tumor sub-group specific candidate biomarkers. Thus, UALCAN web-portal could be extremely helpful in accelerating cancer research. UALCAN is publicly available at http://ualcan.path.uab.edu.

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Author and article information

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 05 November 2020

Publication date Collection: November 2020

Volume: 12

Issue: 11

Electronic Location Identifier: 3269

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; yoelsis.garcia@ 123456vhir.org (Y.G.-M.); cristina.mir@ 123456vhir.org (C.M.); laia.carballo@ 123456alumni.vhir.org (L.C.); joscastellvi@ 123456vhebron.net (J.C.); jtemprana@ 123456vhebron.net (J.T.-S.)

[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; jlorente@ 123456vhebron.net

[4 ]Radiotherapy Unit, Vall d’Hebron Research Institute (VHIR), Autonomous University of Barcelona, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; sbenavente@ 123456vhebron.net

[5 ]Department of Otolaryngology-Head and Neck Surgery, Central University Hospital of Asturias, University of Oviedo, ISPA, IUOPA, 33011 Oviedo, Spain; juanagp@ 123456ispasturias.es (J.M.G.-P.); ynkc1@ 123456hotmail.com (E.A.); jprodrigo@ 123456uniovi.es (J.P.R.)

[6 ]Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Av. Roma SN, 33011 Oviedo, Spain

[7 ]Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Vall d’Hebron Research Institute (VHIR), Passeig Vall d´Hebron 119–129, 08035 Barcelona, Spain

Author notes

[* ]Correspondence: matilde.lleonart@ 123456vhir.org ; Tel.: +34-934894169; Fax: +34-932746708

Author information

Yoelsis Garcia-Mayea https://orcid.org/0000-0002-9395-7471

Josep Castellvi https://orcid.org/0000-0001-5745-9996

Jordi Temprana-Salvador https://orcid.org/0000-0001-9516-1680

Eva Allonca https://orcid.org/0000-0002-2532-5421

Juan P. Rodrigo https://orcid.org/0000-0003-3063-0890

Article

Publisher ID: cancers-12-03269

DOI: 10.3390/cancers12113269

PMC ID: 7694336

PubMed ID: 33167355

SO-VID: 350f3fd7-8e1c-408e-9e4f-e579af5f7400

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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

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Karger: Oncology

Most cited references 56

Cancer statistics, 2019

The PRIDE database and related tools and resources in 2019: improving support for quantification data

UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

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