TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma. (28th February 2018)

• Record Type: Journal Article
• Authors: Bae, Woo-Kyun; Hong, Chang-Soo; Park, Mi-Ra; Sun, Eun-Gene; Lee, Ji-Hee; Kang, Keunsoo; Ryu, Kyung-Hyun; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Chung, Ik-Joo
• Is Part Of: Cancer letters. Volume 415(2018)
• Page Start: 106
• Page End: 116
• Publication Date: 2018-02-28
• Subjects: p73 -- KAI1 -- Invasion -- Migration -- Colorectal cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.12.002
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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. Highlights: TAp73 inhibits invasion, migration and metastasis of colorectal cancer cells. TAp73 directly binds to the KAI1 promoter and induces its expression. KAI1 is indispensable for TAp73-mediated inhibition of cell invasion and migration. TAp73 and KAI1 expression levels are positively correlated in human colorectal cancer.