title: Thyroid hormone receptor β1 suppresses proliferation and migration by inhibiting PI3K/Akt signaling in human colorectal cancer cells.
abstract: Thyroid hormone receptor β1 (TRβ1) is a ligand‑dependent transcription factor that belongs to the superfamily of nuclear receptors. TRβ1 has been found to act as a tumor suppressor in many solid tumors including breast cancer and hepatocellular carcinoma, but its role in the progression of human colorectal cancer (CRC) remains unclear. In this study, microarray data analysis revealed that TRβ1 mRNA was downregulated in CRC tumors compared with that in the normal counterparts in both The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Using a CRC tissue microarray (TMA), we confirmed that the expression of TRβ1 was decreased in human CRC tumor tissues in contrast to normal colorectal mucosal tissues. Notably, the TRβ1 expression was strongly correlated with tumor size (p=0.045). Furthermore, we found that CRC cell proliferation and migration were significantly inhibited by TRβ1 overexpression in vitro. Mechanistic studies indicated that activated phosphorylated Akt was clearly suppressed by TRβ1 in the CRC tissues and cells. In conclusion, this study provides evidence that TRβ1 plays a critical role in the progression of CRC via the PI3K/Akt pathway, and the TRβ1 gene may represent a novel target for CRC therapeutics.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Guangang
authors.initials: G
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100050, P.R. China.
authors.forename: Gejing
authors.initials: G
authors.lastname: De
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt