Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma

Sawanyawisuth, Kanlayanee; Tantapotinan, Nattawat; Wongkham, Chaisiri; Riggins, Gregory J.; Kraiklang, Ratthaphol; Wongkham, Sopit; Puapairoj, Anucha

doi:10.5604/16652681.1184223

Cited by 20 publications

(22 citation statements)

References 30 publications

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“…Other signaling pathways identified in this large screen that has been confirmed in different studies include MAPK/ERK [ 60 , 61 , 62 ], ErbB [ 63 , 64 , 65 ], TGFβ [ 66 ], Wnt/β-catenin [ 66 , 67 ], JAK/STAT [ 68 ], integrin signaling [ 69 , 70 , 71 , 72 ], and adherent and tight junction signaling ( Figure 2 and Figure 3 ). It should also be noted that the downregulation of Akt and MAPK/ERK pathways by Trop2 were also described [ 65 , 73 , 74 , 75 ], suggesting that the effect of Trop2 may be cell context-dependent.…”

Section: Trop2 In Healthy Tissue and Developmentmentioning

confidence: 99%

“…Other miRNAs that target Trop2 were also identified in head-and-neck carcinoma [ 134 ] and urothelial bladder cancer [ 135 ]. Furthermore, we and others showed that Trop2 expression is regulated by methylation of TACSTD2 gene promoter in various cancer cells [ 73 , 75 , 88 , 136 , 137 ]. Importantly, Lin et al found hypermethylation of TACSTD2 gene promoter in lung adenocarcinoma tissues and cell lines explaining low expression of Trop2 in this type of cancer [ 73 ].…”

Section: Trop2 In Cancermentioning

confidence: 99%

“…While the increased Trop2 expression in one lung cancer cell line leads to the suppression of cell proliferation, the silencing of Trop2 in another cell line promotes it. Trop2 knockdown also significantly stimulates cell proliferation and migration in cholangiocarcinoma cell lines and is associated with increased ERK phosphorylation [ 75 ]. Furthermore, knockdown of Trop2 in the cervical cancer cells promotes cell proliferation, migration, and invasion capabilities in vitro and enhances tumor growth capability in vivo [ 77 ].…”

Section: Trop2 In Cancermentioning

confidence: 99%

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Trop2: Jack of All Trades, Master of None

Lenárt

Šmarda

et al. 2020

Cancers

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Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein and an epithelial cell adhesion molecule (EpCAM) family member. Although initially identified as a transmembrane protein, other subcellular localizations and processed forms were described. Its congenital mutations cause a gelatinous drop-like corneal dystrophy, a disease characterized by loss of barrier function in corneal epithelial cells. Trop2 is considered a stem cell marker and its expression associates with regenerative capacity in various tissues. Trop2 overexpression was described in tumors of different origins; however, functional studies revealed both oncogenic and tumor suppressor roles. Nevertheless, therapeutic potential of Trop2 was recognized and clinical studies with drug–antibody conjugates have been initiated in various cancer types. One of these agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this article, we review the current knowledge about the yet controversial function of Trop2 in homeostasis and pathology.

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Section: Trop2 In Healthy Tissue and Developmentmentioning

confidence: 99%

Section: Trop2 In Cancermentioning

confidence: 99%

Section: Trop2 In Cancermentioning

confidence: 99%

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Trop2: Jack of All Trades, Master of None

Lenárt

Šmarda

et al. 2020

Cancers

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“…In breast cancer, membrane localization of TROP2 has been correlated with a poor prognosis while intracellular TROP2 has been associated with increased survival [ 21 ]. TROP2 is silenced by promoter methylation in some tumors and cancer cell lines (bile duct, lung and prostate) [ 22 – 24 ]. However, TROP2 expression has been associated with both inhibition of proliferation [ 22 , 23 ] and increased growth and metastasis [ 20 , 25 – 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…TROP2 is silenced by promoter methylation in some tumors and cancer cell lines (bile duct, lung and prostate) [ 22 – 24 ]. However, TROP2 expression has been associated with both inhibition of proliferation [ 22 , 23 ] and increased growth and metastasis [ 20 , 25 – 30 ]. The role of TROP2 in endocrine-resistant breast cancer has not been evaluated previously.…”

Section: Introductionmentioning

confidence: 99%

TROP2 methylation and expression in tamoxifen-resistant breast cancer

et al. 2018

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BackgroundThe DNA methyltransferase 1 inhibitor, 5-Aza-2′-deoxycytidine (5-Aza-dC) is a potential treatment for breast cancer. However, not all breast tumors will respond similarly to treatment with 5-Aza-dC, and little is known regarding the response of hormone-resistant breast cancers to 5-Aza-dC.MethodsWe demonstrate that 5-Aza-dC-treatment has a stronger effect on an estrogen receptor-negative, Tamoxifen-selected cell line, TMX2-28, than on the estrogen receptor-positive, MCF7, parental cell line. Using data obtained from the HM450 Methylation Bead Chip, pyrosequencing, and RT-qPCR, we identified a panel of genes that are silenced by promoter methylation in TMX2-28 and re-expressed after treatment with 5-Aza-dC.ResultsOne of the genes identified, tumor associated calcium signal transducer 2 (TACSTD2), is altered by DNA methylation, and there is evidence that in some cancers decreased expression may result in greater proliferation. Analysis of DNA methylation of TACSTD2 and protein expression of its product, trophoblast antigen protein 2 (TROP2), was extended to a panel of primary (n = 34) and recurrent (n = 34) breast tumors. Stratifying tumors by both recurrence and ER status showed no significant relationship between TROP2 levels and TACSTD2 methylation. Knocking down TACSTD2 expression in MCF7 increased proliferation however; re-expressing TACSTD2 in TMX2-28 did not inhibit proliferation, indicating that TACSTD2 re-expression alone was insufficient to explain the decreased proliferation observed after treatment with 5-Aza-dC.ConclusionsThese results illustrate the complexity of the TROP2 signaling network. However, TROP2 may be a valid therapeutic target for some cancers. Further studies are needed to identify biomarkers that indicate how TROP2 signaling affects tumor growth and whether targeting TROP2 would be beneficial to the patient.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0589-9) contains supplementary material, which is available to authorized users.

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Liver fluke infection and cholangiocarcinoma: a review

Zheng¹,

Zhu²,

Zhao³

et al. 2016

Parasitol Res

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Parasites are significant groups for carcinogenesis among which liver flukes, including Opisthorchis viverrini and Clonorchis sinensis, are typical representatives causing cholangiocarcinoma (CCA), the second most common primary hepatic malignancy with dismal prognosis. O. viverrini is prevalent in Southeast Asia, infecting 10 million people while C. sinensis has a wider distribution in East Asia and several Southeast Asian countries, affecting more than 35 million people's health. These two worms have some common characteristics and/or discrepancies in life cycle, genome, and transcriptome. As hot spots in recent years, genome and transcriptome research has extracted numerous novel fluke worm-derived proteins, which are excellent for carcinogenic exploration. However, just a handful of these studies have focused on the metabolic pathway. In this study, the main mechanisms of carcinogenesis of both worms, in terms of mechanical damage, metabolic products and immunopathology, and other possible pathways, will be discussed in detail. This review retrospectively describes the main traits of C. sinensis and O. viverrini, their molecular biology and core carcinogenic mechanisms in a contrast pattern.

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Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma

Cited by 20 publications

References 30 publications

Trop2: Jack of All Trades, Master of None

Trop2: Jack of All Trades, Master of None

TROP2 methylation and expression in tamoxifen-resistant breast cancer

Liver fluke infection and cholangiocarcinoma: a review

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