Twisted Gastrulation BMP Signaling Modulator 1 Regulates Papillary Thyroid Cancer Cell Motility and Proliferation

Abstract

Bone morphogenetic proteins (BMPs) are growth factors that have important functions in cell proliferation, migration and differentiation. To date, BMP pathway activation has been found in multiple human tumors and is associated with enhanced malignant tumor growth and metastasis. BMP activity is tightly regulated by a family of soluble extracellular secreted BMP modulators. Twisted gastrulation BMP signaling modulator 1 (TWSG1) is a direct BMP regulator that is required for the full signaling activity of BMPs. However, the functions and mechanisms of TWSG1 in papillary thyroid cancer (PTC) metastasis have not been reported. TWSG1 expression was detected in 44 PTC tissues with lymph node metastasis (LNM) and 56 PTC tissues without LNM using quantitative real-time polymerase chain reaction (qRT-PCR). Gain- and loss-of-function approaches were used to assess the biological function of TWSG1 in PTC cells. Matrigel assays demonstrated the effect of tumor cell-derived TWSG1 on endothelial cell function. Our results showed that TWSG1 expression was significantly enhanced in PTC with LNM compared to that in PTC without LNM. TWSG1 knockdown inhibited migration, invasion and proliferation of PTC cells. Additionally, TWSG1 suppression impaired the tumor cell-induced endothelial cell sprout formation. We found that TWSG1 signaling may be transduced by the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 2 and 9. In conclusion, TWSG1 was highly expressed in metastasized PTC; tumor growth, migration and invasion were dependent on TWSG1, and it may be a new diagnostic and therapeutic target for PTC.

Novel role of ASH1L histone methyltransferase in anaplastic thyroid carcinoma

“…A subset of these genes with known pro-oncogenic associations is listed in Table 2 and is briefly described. CCAT1, TWSG1, HAPL1, and NNMT are overexpressed in various malignancies in which they promote cancer cell proliferation, migration, and invasion (28)(29)(30)(31)(32). CCAT1 encodes a long noncoding RNA (lncRNA).…”

Hsa_Circular RNA_0001013 Exerts Oncogenice Effects in Gastric Cancer via the MicroRNA-136/TWSG1 Axis

“…Further analysis in our research elucidated that TWSG1 was upregulated in GC tissues, and that miR-136 overexpression led to decreased GC cell proliferation, invasion, and migration and enhanced cell cycle arrest and apoptosis by downregulating TWSG1. Consistently, PTC tissues contained upregulated TWSG1, and TWSG1 knockdown depressed migration, invasion and proliferation of PTC cells [12]. In addition, the research conducted by Liu et al elaborated that TWSG1 expression was substantially augmented in glioma tissues versus normal brain tissue, and that TWSG1 upregulation caused enhancement of glioma cell proliferation [27].…”

“…However, the interaction between hsa_circ_0001013 and miR-136 was scarcely investigated. Besides, Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been detected as an oncogene in papillary thyroid cancer (PTC) [12]. However, it is unde ned about the interaction between miR-136 and TWSG1 in GC development.…”

Duality of bone morphogenetic proteins in cancer: A comprehensive analysis

“…In the case of gastric and colorectal cancer cells, TWSG overexpression was reported to reduce the cancerous growth and development by regulating BMP signaling (Gylfe et al, 2013; Yuan et al, 2018). In contrast, knockdown of TWSG is related to inhibition of papillary thyroid cell migratory and invasive properties by regulating the levels of proteins such as ID‐1, P‐SMAD 1/5 involved in the BMP signaling pathway (S. Xia et al, 2017). Follistatin (FST) with its antagonistic effects is best known for Activins, but it has also been found to have an affinity toward BMP7 and can inhibit its functioning (Yamashita et al, 1995).…”