N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release

Kamble, Pradnya R; Patkar, Shivali; Breed, Ananya A.; Pathak, Bhakti R.

doi:10.1016/j.abb.2021.109084

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…The transmembrane protein Trop-2 possesses four putative N-linked glycosylation sites (N-33, N-120, N-168, and N-208) located in the extracellular domain [77]. Direct mutagenesis experiments targeting different sites revealed that N-120 and N-208 play critical roles in ligand binding and exosomal release, while leaving surface expression unaffected [78]. While the aberrant glycosylation status of Trop-2 was not explored in cancer, aberrant glycosylation distribution was confirmed in transformed keratinocytes compared to normal cells [79].…”

Section: Trop-2mentioning

confidence: 99%

Cancer Stem Cell Metastatic Checkpoints and Glycosylation Patterns: Implications for Therapeutic Strategies

Aghamiri,

Amin

2024

Kinases and Phosphatases

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Cancer stem cells (CSCs), found within tumors, are powerful drivers of disease recurrence and metastasis. Their abilities to self-renew and maintain stem-like properties make treatment difficult, as their heterogeneity and metastatic properties can lead to resistance and limit the effectiveness of standard therapies. Given their significance, CSCs are typically isolated based on combinations of markers, which often indicate heterogeneous populations of CSCs. The lack of consensus in cell characterization poses challenges in defining and targeting these cells for effective therapeutic interventions. In this review, we suggest five promising molecules—ABCB5, CD26, CD66c, uPAR, and Trop-2—chosen specifically for their distinct distribution within cancer types and clinical relevance. These markers, expressed at the cell surface of CSCs, could significantly enhance the specificity of cancer stemness characterization. This review focuses on describing their pivotal roles as biomarker checkpoints for metastasis. Additionally, this review outlines existing literature on glycosylation modifications, which present intriguing epitopes aimed at modulating the stability and function of these markers. Finally, we summarize several promising in vivo and clinical trial approaches targeting the mentioned surface markers, offering potential solutions to overcome the therapeutic resistance of CSCs and addressing current gaps in treatment strategies.

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Section: Trop-2mentioning

confidence: 99%

Cancer Stem Cell Metastatic Checkpoints and Glycosylation Patterns: Implications for Therapeutic Strategies

Aghamiri,

Amin

2024

Kinases and Phosphatases

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“…Trop-2 and EpCAM are cell adhesion molecules that are structurally different from the other four known molecules, integrins, cadherins, selectins, and immunoglobulin CAMs [ 20 ]. Trop-2 participates in tight junction and basal membrane integrity [ 21 ]. Although it is not fully known, it has been shown that Trop-2 has many functions in the cell that are not related to cell adhesion, such as proliferation, invasion, and stemness [ 22 , 23 ].…”

Section: Functions Of Trop-2mentioning

confidence: 99%

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

Koltai,

Fliegel

2023

IJMS

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Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non-epithelial tumors. Trop-2 is an intracellular calcium signal transducer that participates in the promotion of cell proliferation, migration, invasion, metastasis, and probably stemness. It also has some tumor suppressor effects. The pro-tumoral actions have been thoroughly investigated and reported. However, Trop-2’s activity in chemoresistance is less well known. We review a possible relationship between Trop-2, chemotherapy, and chemoresistance. We conclude that there is a clear role for Trop-2 in some specific chemoresistance events. On the other hand, there is no clear evidence for its participation in multidrug resistance through direct drug transport. The development of antibody conjugate drugs (ACD) centered on anti-Trop-2 monoclonal antibodies opened the gates for the treatment of some tumors resistant to classic chemotherapies. Advanced urothelial tumors and breast cancer were among the first malignancies for which these ACDs have been employed. However, there is a wide group of other tumors that may benefit from anti-Trop-2 therapy as soon as clinical trials are completed.

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“…Trop-2-containing cancer cells are also involved in intercellular or cellular-matrix communication via an exosome release and transport. [26][27][28][29][30] The findings of research related to Trop-2-containing exosomes in cancer pathogenesis and progression or therapeutic applications from other epithelial cancers were helpful for generating hypotheses in breast cancer. For example, it would be interesting to investigate the details, functionality, and impact on breast cancer progression of different exosomes with specific cargo payloads released from Trop-2 positive cells.…”

Section: Opinionmentioning

confidence: 99%

Trop-2-Cells, Their Exosomal Cargo, and the Potential Impact on Diagnostics and Therapeutics in Breast Cancer: The Expanding Frontiers

Kok¹

2022

Explor Res Hypothesis Med

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Recently, an anti-trophoblast surface antigen-2 (Trop-2) antibody-drug conjugate targeting Trop-2 positive cancer cells has been approved for treating patients with unresectable locally advanced or metastatic triple-negative breast cancer, who have failed two or more lines of systemic chemotherapy. This has renewed the interest in translational research of Trop-2 positive breast cancer, the gene TACSTD2 and microRNAs that interact with it, and the signaling networks sparked by Trop-2 mediated signaling. In addition, this opinion paper argues that exosomes, extracellular vesicles that are released from Trop-2 positive cancer cells, could play a significant role in cancer progression. Furthermore, diagnostic applications using Trop-2-released exosomes, the cargo exosomes carry, which could be any genetic information such as specific miRNAs, adhesion molecules such as integrins, and metabolites, are yet to be explored in breast cancer patients. Most of the evidence and data are obtained from studies in epithelial cancers other than breast cancers, which have been introduced in the current paper. Therefore, this article briefly summarizes previously published data on other cancer types, forms some hypotheses, and proposes research questions and directions that may be explored further.

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N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release

Cited by 9 publications

References 38 publications

Cancer Stem Cell Metastatic Checkpoints and Glycosylation Patterns: Implications for Therapeutic Strategies

Cancer Stem Cell Metastatic Checkpoints and Glycosylation Patterns: Implications for Therapeutic Strategies

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

Trop-2-Cells, Their Exosomal Cargo, and the Potential Impact on Diagnostics and Therapeutics in Breast Cancer: The Expanding Frontiers

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