Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells

Yong Sun Maeng, Rina Lee, Boram Lee, Seung Il Choi, Eung Kweon Kim

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Metastasis is the main cause of mortality in cancer patients. Although there are many anti-cancer drugs targeting tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression; in particular, lymphangiogenesis is pivotal for metastasis in cancer. Here we report that lithium inhibits colon cancer metastasis by blocking lymphangiogenesis. Lithium reduces the expression of transforming growth factor-β-induced protein (TGFBIp) in colon cancer cells by inhibiting Smad3 phosphorylation via GSK3β inactivation. Moreover, lithium inhibits lymphatic endothelial cell migration, which is increased upon TGFBIp expression in tumor cells. Lithium had no significant effect on SW620 tumor growth in vitro and in vivo; however, it inhibited lymphangiogenesis in tumors. In tumor xenografts model, lithium was found to prevent metastasis to the lungs, liver, and lymph nodes by inhibiting TGFBIp-induced tumor lymphangiogenesis. Collectively, our findings demonstrate a novel role of lithium in the inhibition of colon cancer metastasis by blocking TGFBIp expression, and thereby TGFBIp-induced lymphangiogenesis, in primary tumors.

Original languageEnglish
Article number20739
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Feb 9

Bibliographical note

Funding Information:
This research was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF 2014R1A1A2057458) and a grant from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (No. 2011-0028699).

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells'. Together they form a unique fingerprint.

Cite this