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

Abstract

Background/Aim: Resistance to anoikis is a prerequisite step in metastasis, a major cause of death in patients with cancer, including thyroid cancer. Impairing anoikis resistance is a possible strategy for therapy of metastatic cancer. We, therefore, we aimed to investigate the key players of anoikis resistance. Materials and Methods: Papillary-type (BCPAP), follicular-type (FTC133), and anaplastic-type (ARO) thyroid carcinoma cells, cultured in poly(2-hydroxyethyl methacrylate)-coated plates to mimic circulating cells, were used as model systems in this study. Flow cytometry and softagar assays were used to determine cells exhibiting anoikis resistance. Proteomics was used to identify candidate proteins and validated using western blot and siRNA knockdown. Results: Only ARO cells showed both anoikis resistance potential and anchorage-independent growth ability. Tumor susceptibility gene 101 protein (TSG101) was identified to be potentially important in anoikis resistance, which was confirmed by an increase in anoikis and expression of a proapoptotic protein (BCL-2 like protein 4) and an apoptotic marker (cleaved poly-ADP ribose polymerase) in floating siTSG101-knockdown cells. Conclusion: To our knowledge, this is the first study that implicates the importance of TSG101 in anoikis resistance of thyroid cancer.

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

“…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.…”

“…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.…”

Moonlighting Role of PEDF in Breast Cancer

“…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.…”

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

“…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 ).…”