The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

Erfani, Sonia F.; Hua, Hui; Pan, Yueyin; Zhou, Binhua P.; Yang, Xiuwei H.

doi:10.3390/cancers13092005

Cited by 15 publications

(7 citation statements)

References 163 publications

(362 reference statements)

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“…These tetraspanins can bind with surface proteins and other molecules at the plasma membrane in tetraspanin-enriched membrane microdomains (TEMs). By interacting with integrins, receptor molecules, and other signaling intermediaries, tetraspanins can activate downstream signaling to control key physiological processes including apoptosis, adhesion, differentiation, oncogenesis, and metastatic tumor progression (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway

et al. 2022

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ObjectAt present, there are few effective treatment options available to patients suffering from osteosarcoma (OS). Clarifying the signaling pathways that govern OS oncogenesis may highlight novel approaches to treating this deadly form of cancer. Recent experimental evidence suggests that the transmembrane protein tetraspanin-9 (Tspan9) plays a role in tumor development. This study was thus formulated to assess the molecular role of Tspan9 as a regulator of OS cell metastasis.MethodsGene expression in OS cell lines was evaluated via qRT-PCR, while CCK-8, colony formation, Transwell, and wound healing assays were used to explore the in vitro proliferative, invasive, and migratory activities of OS cells. The relationship between Tspan9 and in vivo OS cell metastasis was assessed by injecting these cells into the tail vein of nude mice. Interactions between the Tspan9 and integrin β1 proteins were explored through mass spectrometric and co-immunoprecipitation, and Western blotting to assess the functional mechanisms whereby Tspan9 shapes OS pathogenesis.ResultsBoth primary OS tumors and OS cell lines commonly exhibited Tspan9 upregulation, and the knockdown of this tetraspanin suppressed the migration, invasion, and epithelial-mesenchymal transition (EMT) activity in OS cells, whereas Tspan9 overexpression resulted in opposite phenotypes. Tumor lung metastasis were significantly impaired in mice implanted with HOS cells in which Tspan9 was downregulated as compared to mice implanted with control HOS cells. Tspan9 was also found to interact with β1 integrin and to contribute to OS metastasis via the amplification of integrin-mediated downstream FAK/Ras/ERK1/2 signaling pathway.ConclusionThese data suggest that Tspan9 can serve as a promising therapeutic target in OS.

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Section: Introductionmentioning

confidence: 99%

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway

et al. 2022

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“…The MS heatmap presented integrins and transferrin receptor 1 as promising candidates for mediating 5A6 antimetastatic effects on MDA-MB-231 cells ( Dataset S1 ). The interaction of different integrins with tetraspanins and their involvement in tumor metastasis are gaining interest ( 27 – 29 ), and transferrin receptor 1 has also been noted to be an antimetastatic therapeutic target ( 30 , 31 ). We knocked out the integrins expressed in MDA-MB-231 cells and transferrin receptor 1 using CRISPR/CAS9 ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

The molecular mechanism of CD81 antibody inhibition of metastasis

Abu-Saleh

Kuo

Jiang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Metastases are reduced in CD81KO mice. In addition, a unique anti-CD81 antibody, 5A6, inhibits metastasis in vivo and invasion and migration in vitro. Here, we probed the structural components of CD81 required for the antimetastatic activity induced by 5A6. We found that the removal of either cholesterol or the intracellular domains of CD81 did not affect inhibition by the antibody. We show that the uniqueness of 5A6 is due not to increased affinity but rather to its recognition of a specific epitope on the large extracellular loop of CD81. Finally, we present a number of CD81 membrane-associated partners that may play a role in mediating the 5A6 antimetastatic attributes, including integrins and transferrin receptors.

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“…Tetraspanins are multifunctional transmembrane proteins involved, among others, in the regulation of adhesion, integrin signaling, metalloproteinase activity and antigen presentation. They can also act as tumor suppressors or oncogenic proteins by regulating proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) [ 58 , 59 , 60 , 61 , 62 ]. It is worth noting, however, that many tetraspanins have different functions depending on the type of cancer.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?

Grzanka

Stachurska-Skrodzka

Adamiok‐Ostrowska

et al. 2022

IJMS

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Extracellular vesicles (EVs) are small, membranous structures involved in intercellular communication. Here, we analyzed the effects of thyroid cancer-derived EVs on the properties of normal thyroid cells and cells contributing to the tumor microenvironment. EVs isolated from thyroid cancer cell lines (CGTH, FTC-133, 8505c, TPC-1 and BcPAP) were used for treatment of normal thyroid cells (NTHY), as well as monocytes and endothelial cells (HUVEC). EVs’ size/number were analyzed by flow cytometry and confocal microscopy. Gene expression, protein level and localization were investigated by qRT-PCR, WB and ICC/IF, respectively. Proliferation, migration and tube formation were analyzed. When compared with NTHY, CGTH and BcPAP secreted significantly more EVs. Treatment of NTHY with cancer-derived EVs changed the expression of tetraspanin genes, but did not affect proliferation and migration. Cancer-derived EVs suppressed tube formation by endothelial cells and did not affect the phagocytic index of monocytes. The number of 6μm size fraction of cancer-derived EVs correlated negatively with the CD63 and CD81 expression in NTHY cells, as well as positively with angiogenesis in vitro. Thyroid cancer-derived EVs can affect the expression of tetraspanins in normal thyroid cells. It is possible that 6 μm EVs contribute to the regulation of NTHY gene expression and angiogenesis.

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The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

Cited by 15 publications

References 163 publications

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway

The molecular mechanism of CD81 antibody inhibition of metastasis

Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?

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