Tumor Susceptibility Gene 101 Mediates Anoikis Resistance of Metastatic Thyroid Cancer Cells

Saharat, Kittirat; Lirdprapamongkol, Kriengsak; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Svasti, Jisnuson; Paricharttanakul, N. Monique

doi:10.21873/cgp.20106

Cited by 9 publications

(14 citation statements)

References 31 publications

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“…Here, we demonstrated that cancer-specific byproduct TSG∆154-1054 stabilizes TSG101 protein, and thus it promotes tumor cell aggression in terms of proliferative, migratory, and metastatic activities. Recent TSG101 knockdown experiments implicated the function of TSG101 protein in anoikis (cell-detachment-induced apoptosis) resistance of thyroid cancer, which is a prerequisite for metastasis [42]. It is of interest to examine the activation of anoikis in TSGΔ154-1054-siRNA transfected cells in which TSG101 protein is upregulated.…”

Section: Discussionmentioning

confidence: 99%

“…It is of interest to examine the activation of anoikis in TSGΔ154-1054-siRNA transfected cells in which TSG101 protein is upregulated. Since we found no activation of caspase 8 in these knockdown cells, a proapoptotic protein (BCL-2 like protein 4) and an apoptotic marker (cleaved poly-ADP ribose polymerase) may function in anoikis [42] through caspase 8-independent pathways.…”

Section: Discussionmentioning

confidence: 99%

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Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma

Chua

Kameyama

Mayeda

et al. 2019

IJMS

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TSG101 (Tumor susceptibility 101) gene and its aberrantly spliced isoform, termed TSG101∆154-1054, are tightly linked to tumorigenesis in various cancers. The aberrant TSG101∆154-1054 mRNA is generated from cancer-specific re-splicing of mature TSG101 mRNA. The TSG101∆154-1054 protein protects the full-length TSG101 protein from ubiquitin-mediated degradation, implicating TSG101∆154-1054 protein in the progression of cancer. Here, we confirmed that the presence of TSG101∆154-1054 mRNA indeed caused an accumulation of the TSG101 protein in biopsies of human nasopharyngeal carcinoma (NPC), which was recapitulated by the overexpression of TSG101∆154-1054 in the NPC cell line TW01. We demonstrate the potential function of the TSG101∆154-1054 protein in the malignancy of human NPC with scratch-wound healing and transwell invasion assays. By increasing the stability of the TSG101 protein, TSG101∆154-1054 specifically enhanced TSG101-mediated TW01 cell migration and invasion, suggesting the involvement in NPC metastasis in vivo. This finding sheds light on the functional significance of TSG101∆154-1054 generation via re-splicing of TSG101 mRNA in NPC metastasis and hints at its potential importance as a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma

Chua

Kameyama

Mayeda

et al. 2019

IJMS

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“…All these proteins have been involved in different metastatic processes, and could be a target for new therapies but, more interestingly, they can be indicators of the process' progress and could suggest what the mechanism and the signalling pathway of these cells involved in the resistance to chemotherapeutic treatments is. One of the cellular mechanisms that may be involved in these resistance processes is anoikis [24][25][26][27][28]. Anoikis is a form of apoptosis that occurs in anchorage-dependent cells and in a niche context, when the cells detach from the surrounding extracellular matrix (ECM) and lose the connection to the nurse surrounding cells [28,29]; this is one of the processes we observed after the combination of chemotherapy and treatment with the carboxy-terminal part of PEDF protein.…”

Section: Introductionmentioning

confidence: 89%

Moonlighting Role of PEDF in Breast Cancer

Gil-Gas

Sánchez‐Díez

Honrubia-Gómez

et al. 2020

Preprint

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Background: Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates still remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods: We have designed a transgenic protein consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Present work is based in doses-response in vitro assays as well as flow cytometry analysis of surface markers and cell cycle kinetic study of the tumour initiating cells.Results: In this study we show that this type of cells is present not only in cancer cell lines but also in cancer cells from patients with metastatic and advanced stage tumours. We also present new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, expression of markers, and carcinogenicity of cancer stem cells. This protein has been involved in self-renewal in adult stem cells and has been described as anti-tumoral because of its anti-angiogenic effect. However, we show that PEDF enhances resistance in breast cancer patient cells in vitro culture by favoring a slow cellular cycle population (LT+). The PEDF signalling pathway could be a useful tool for controlling cancer stem cells self-renewal, and therefore control patient relapse. Conclusions: We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in vitro culture. We have also demonstrated that this PEDF modified protein produces a significant decrease in cancer stem cell markers. All these properties make this protein a potential application in clinical cancer therapies via co-administration with chemotherapy for relapse cancer treatment.

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“…Furthermore, anoikis resistance has also been demonstrated to play an important role in metastatic thyroid cancer. Kittirat Saharat and colleagues have reported that tumor susceptibility gene 101 protein (TSG101) was identified to be upregulated in anoikis resistant thyroid cancer cells, which was accompanied with decreased expression of an apoptotic marker (cleaved poly-ADP ribose polymerase) and a pro-apoptotic protein (BCL-2 like protein 4) ( 8 ). Our previous study revealed that anoikis resistance induced by miR-424-5p promoted lung metastasis of thyroid cancer by inactivating Hippo signaling via simultaneously targeting WWC1, SAV1, and LAST2 ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p

Liu

Bian

et al. 2021

Front. Oncol.

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The principal issue derived from thyroid cancer is its high propensity to metastasize to the lymph node. Aberrant exprssion of long non-coding RNAs have been extensively reported to be significantly correlated with lymphatic metastasis of thyroid cancer. However, the clinical significance and functional role of lncRNA-MAPK8IP1P2 in lymphatic metastasis of thyroid cancer remain unclear. Here, we reported that MAPK8IP1P2 was downregulated in thyroid cancer tissues with lymphatic metastasis. Upregulating MAPK8IP1P2 inhibited, while silencing MAPK8IP1P2 enhanced anoikis resistance in vitro and lymphatic metastasis of thyroid cancer cells in vivo. Mechanistically, MAPK8IP1P2 activated Hippo signaling by sponging miR-146b-3p to disrupt the inhibitory effect of miR-146b-3p on NF2, RASSF1, and RASSF5 expression, which further inhibited anoikis resistance and lymphatic metastasis in thyroid cancer. Importantly, miR-146b-3p mimics reversed the inhibitory effect of MAPK8IP1P2 overexpression on anoikis resistance of thyroid cancer cells. In conclusion, our findings suggest that MAPK8IP1P2 may serve as a potential biomarker to predict lymphatic metastasis in thyroid cancer, or a potential therapeutic target in lymphatic metastatic thyroid cancer.

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Tumor Susceptibility Gene 101 Mediates Anoikis Resistance of Metastatic Thyroid Cancer Cells

Cited by 9 publications

References 31 publications

Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma

Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma

Moonlighting Role of PEDF in Breast Cancer

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p

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