Tetraspanins: Physiology, Colorectal Cancer Development, and Nanomediated Applications

Ţîţu, Ştefan; Grapa, Cristiana; Mocan, Teodora; Bălăcescu, Ovidiu; Irimie, Alexandru

doi:10.3390/cancers13225662

Cited by 12 publications

(16 citation statements)

References 87 publications

(103 reference statements)

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“…Clinically approved drugs often have limitations in target accumulation due to their lack of specificity, resulting in modest efficacy and numerous adverse effects. To enhance their potential, researchers utilize various targeting molecules, with Tspan proteins exhibiting significant promise in this regard [ 109 ]. Yue et al were the first to demonstrate the binding of Andrographis paniculata water (APW), including its components Andrographis paniculata Lactone, Andrographis paniculata A, and Andrographis paniculata C, to Tspan28, resulting in the inhibition of its function.…”

Section: The Role Of the Tspan Protein Family In Cancer Treatmentmentioning

confidence: 99%

Tspan protein family: focusing on the occurrence, progression, and treatment of cancer

Zhang,

Song,

Shang

et al. 2024

Cell Death Discov.

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The Tetraspanins (Tspan) protein family, also known as the tetraspanin family, contains 33 family members that interact with other protein molecules such as integrins, adhesion molecules, and T cell receptors by forming dimers or heterodimers. The Tspan protein family regulates cell proliferation, cell cycle, invasion, migration, apoptosis, autophagy, tissue differentiation, and immune response. More and more studies have shown that Tspan proteins are involved in tumorigenesis, epithelial-mesenchymal transition, thrombosis, tumor stem cell, and exosome signaling. Some drugs and microRNAs can inhibit Tspan proteins, thus providing new strategies for tumor therapy. An in-depth understanding of the functions and regulatory mechanisms of the Tspan protein family, which can promote or inhibit tumor development, will provide new strategies for targeted interventions in the future.

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Section: The Role Of the Tspan Protein Family In Cancer Treatmentmentioning

confidence: 99%

Tspan protein family: focusing on the occurrence, progression, and treatment of cancer

Zhang,

Song,

Shang

et al. 2024

Cell Death Discov.

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“…In the context of cancer, tetraspanins have been implicated in tumor progression, metastasis, and resistance to therapy [5,6]. By forming protein complexes with various cell surface molecules, such as integrins and receptors, tetraspanins participate in the progression and metastasis of various cancers, including CC (Scheme S1, Supplementary File S1) [5,7,8]. In CC, various studies have shown specific expressions of some tetraspanins in CC cell lines and bulk tissues, indicating their potential as diagnostic markers and therapeutic Life 2024, 14, 126 2 of 16 targets [7,9,10].…”

Section: Introductionmentioning

confidence: 99%

“…By forming protein complexes with various cell surface molecules, such as integrins and receptors, tetraspanins participate in the progression and metastasis of various cancers, including CC (Scheme S1, Supplementary File S1) [5,7,8]. In CC, various studies have shown specific expressions of some tetraspanins in CC cell lines and bulk tissues, indicating their potential as diagnostic markers and therapeutic Life 2024, 14, 126 2 of 16 targets [7,9,10]. Some tetraspanins, such as TSPAN8 and CD151, have been associated with advanced tumor stage, metastasis, and poor clinical outcomes [7,11,12].…”

Section: Introductionmentioning

confidence: 99%

Spatial Transcriptomic Profiling of Tetraspanins in Stage 4 Colon Cancer from Primary Tumor and Liver Metastasis

Suwatthanarak,

Thanormjit,

Suwatthanarak

et al. 2024

Life

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Stage 4 colon cancer (CC) presents a significant global health challenge due to its poor prognosis and limited treatment options. Tetraspanins, the transmembrane proteins involved in crucial cancer processes, have recently gained attention as diagnostic markers and therapeutic targets. However, their spatial expression and potential roles in stage 4 CC tissues remain unknown. Using the GeoMx digital spatial profiler, we profiled all 33 human tetraspanin genes in 48 areas within stage 4 CC tissues, segmented into immune, fibroblast, and tumor compartments. Our results unveiled diverse gene expression patterns across different primary tumor sub-regions. CD53 exhibited distinct overexpression in the immune compartment, hinting at a potential role in immune modulation. TSPAN9 was specifically overexpressed in the fibroblast compartment, suggesting involvement in tumor invasion and metastasis. CD9, CD151, TSPAN1, TSPAN3, TSPAN8, and TSPAN13 displayed specific overexpression in the tumor compartment, indicating potential roles in tumor growth. Furthermore, our differential analysis revealed significant spatial changes in tetraspanin expression between patient-matched stage 4 primary CC and metastatic liver tissues. These findings provide spatially resolved insights into the expression and potential roles of tetraspanins in stage 4 CC progression, proposing their utility as diagnostic markers and therapeutic targets. Understanding this landscape is beneficial for tailoring therapeutic strategies to specific sub-tumor regions in the context of stage 4 CC and liver metastasis.

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“…Over the past ten years, the implication of tetraspanins in cancer has been largely documented and several of these proteins are considered as valid targets for the design of novel anticancer agents. They are particularly adapted to the treatment of colorectal cancer, hepatocellular carcinoma, gastric cancer and other types of solid tumors [ 6 , 7 , 8 , 9 ]. These proteins are also considered in onco-hematology, notably for the treatment of acute myeloid leukemia (AML) and lymphoma [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…There are over 33 tetraspanins in humans, plus non-conventional forms generated by alternative splicing [ 3 , 15 ]. Many of these tetraspanins are involved in cancers, chiefly TSPAN1, TSPAN8, TSPAN 13, CD9, CD37, CD63, CD81, CD82 and CD151 [ 6 ]. The latter protein CD151 can be targeted with monoclonal antibodies to block both primary tumor growth and metastasis in xenograft cancer models [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

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Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

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Tetraspanins: Physiology, Colorectal Cancer Development, and Nanomediated Applications

Cited by 12 publications

References 87 publications

Tspan protein family: focusing on the occurrence, progression, and treatment of cancer

Tspan protein family: focusing on the occurrence, progression, and treatment of cancer

Spatial Transcriptomic Profiling of Tetraspanins in Stage 4 Colon Cancer from Primary Tumor and Liver Metastasis

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

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