Abstract
The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis.
Highlights
The Inhibitor of Growth (ING) proteins (ING1ING5) have been identified and characterized as candidate tumor suppressors
Further study showed that ING5 overexpression inhibited epithelial-to-mesenchymal transition (EMT) indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT-inducing genes including CEACAM6, BMP2 and CDH11
The results showed that ING5 overexpression significantly inhibited cell proliferation and colony formation abilities of A549 cells, whereas these effects were promoted by ING5 knockdown in H1299 cells (Figure 2A, 2B)
Summary
The Inhibitor of Growth (ING) proteins (ING1ING5) have been identified and characterized as candidate tumor suppressors. All ING proteins share a highly conserved carboxy-terminal plant homeodomain (PHD) and are involved in the control of cell growth, senescence, apoptosis, DNA repair and chromatin remodeling [13]. The pilot study of ING5 has shown that it physically interacts with p300 and p53, and overexpression of ING5 induces apoptosis in colorectal cancer cells [4]. Doyon Y et al [5] have revealed that ING5 associates with HBO1 and MOZ/MORF to form two distinct HAT complexes, which interact with the MCM helicase and are essential for DNA replication in human cells during S phase. Our previous study [6] indicates that ING5 overexpression in MEF cells inhibits cell growth, induces a delay in www.impactjournals.com/oncotarget
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
