TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma
| Autor: | Eun Gene Sun, Jun-Eul Hwang, Sang-Hee Cho, Mi-Ra Park, Hyun-Jeong Shim, Kyung-Hyun Ryu, Woo Kyun Bae, Keunsoo Kang, Chang-Soo Hong, Ik-Joo Chung, Ji-Hee Lee |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer Nerve Tissue Proteins Mice SCID Biology law.invention Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement Mice Inbred NOD Transcription (biology) law Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Transcription factor Mice Knockout Cell invasion Extracellular Matrix Proteins Gene knockdown Tumor Protein p73 HCT116 Cells medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic HEK293 Cells 030104 developmental biology Oncology Apoptosis Doxycycline 030220 oncology & carcinogenesis Cancer research Suppressor Caco-2 Cells Colorectal Neoplasms HT29 Cells |
| Zdroj: | Cancer Letters. 415:106-116 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2017.12.002 |
| Popis: | p73 is a member of the p53 family of transcription factors and, like p53, plays a role as a tumor suppressor. p73 is involved in development, proliferation, apoptosis and metastasis. However, the precise molecular mechanisms underlying its function in inhibiting metastasis remain largely unknown. Here, we show that induction of TAp73 decreased invasion and migration activity of colorectal cancer cells, whereas knockdown of TAp73 led to increased invasion and migration activity. KAI1 was identified as a transcriptional target of TAp73 and its expression is indispensable for TAp73-mediated inhibition of cell invasion and migration. Furthermore, induction of TAp73 in colorectal cancer cells elevated KAI1 expression and decreased the frequency of hepatic metastasis in vivo. Whereas, the decreased invasion and migration activities caused by TAp73 induction were abrogated by knockdown of KAI1. Interestingly, TAp73 and KAI1 are overexpressed in primary colorectal cancers and a significant correlation between TAp73 and KAI1 expression was detected, but their expressions were significantly down-regulated in metastatic cancers. Taken together, our results support a novel role for TAp73 in controlling colorectal cancer cell invasion, migration and metastasis by regulating transcription of KAI1. |
| Databáze: | OpenAIRE |
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