ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer.
A literature search of the PubMed and EMBASE databases was performed using keywords such as "ATM gene" and "lung cancer," and the deadline "October 15 (th), 2016."
A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015).
Analyses of ATM serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination revealed that ATM and ATR kinase activation and FA pathway signaling are intact in the lung cancer cell lines examined.
At the same time, the ATM gene and its encoding product ATM protein predicts the response to radiotherapy, chemotherapy, and prognosis of lung cancer, thus suggesting that the ATM gene may be a new potential target for the diagnosis and treatment of lung cancer.
For instance, ATM (ataxia telangiectasia mutated) SNPs have been associated with increased risk of breast, prostate, leukaemia, colon and early-onset lung cancer, and the intron 3 16-bp repeat in TP53 (tumour protein 53) is associated with an increased risk of lung cancer.
Hence, ATM modulates vimentin expression to facilitate IL-6-induced epithelial-mesenchymal transition and metastasis in lung cancer, indicating that ATM and vimentin might be potential therapeutic targets for inflammation-associated lung cancer metastasis.
However, no good correlation was found either between ATM protein expression and IR-induced MTM or between ATM protein expression and IR-induced MNR in lung cancer patients.
In conclusion, our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs961591-GLTSCR1 rs1035938 on Chr19q13.3, interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592, and synergistic action of PPP1R13L rs1970764 and ATMrs11212592 may associate with lung cancer risk in the Chinese population.
Our results provide evidence that the A allele of ATMrs652311 may be associated with lung cancer risk, and may enhance the effects of smoking habit on lung cancer development.
RanBP9 stable silencing in three different lung cancer cell lines significantly affects the DNA Damage Response (DDR), resulting in delayed activation of key components of the cellular response to IR such as ATM itself, Chk2, γH2AX, and p53.
SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATMrs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1 rs25487, and PMS1 rs5742933.
Taken together, these findings demonstrate that IL-6 inducing ATM phosphorylation increases the expression of MMP-3/MMP-13, augments the abilities of cell migration, and promotes lung cancer metastasis, indicating that ATM is a potential target molecule to overcome IL-6 correlated lung cancer metastasis.
The use of RAD-ADAPT is demonstrated using an example that examines the impact of pharmacologic ATM and ATR kinase inhibition on human lung cancer cell line A549 after ionizing radiation.