The human EWS gene encodes a putative RNA binding protein. As a result of acquired chromosome rearrangement, the N-terminal portion of the EWS protein is fused to the DNA binding domain of either FLI-1 or ERG in the Ewing family of tumors and to the DNA binding domain of ATF1 in malignant melanoma of soft parts. We have determined the cDNA sequence of the mouse Ews gene. Its nucleotide sequence and its translation product demonstrate 93 and 98% homology with the human EWS cDNA and protein, respectively. The murine Ews locus lies within a conserved synteny segment between human chromosome 22q12 and mouse chromosome 11A1-A3.

The invertase mutant defective in the glucose signaling pathway of Schizosaccharomyces pombe (ird11) is resistant to glucose repression. This mutant is able to consume sucrose alongside glucose and grows in glucose-containing media with a generation time close to that of the wild type. Intracellular oxidation, protein carbonyl, and reduced glutathione levels and catalase, superoxide dismutase, and glutathione peroxidase activity were investigated in ird11, to determine the relationship between oxidative stress response and glucose signaling. The expression profiles of some genes involved in regulation of glucose repression (fbp1, fructose-1,6-bis-phosphatase; hxk2, hexokinase) and stress response (atf1 and pap1 transcription factors; ctt1, catalase; sod1, Cu,Zn superoxide dismutase) were analyzed using the quantitative real-time PCR technique. Oxidative stress response in ird11 seems to be affected by glucose signaling in a manner different from that caused by glucose deprivation.

Azole antifungals directly inhibit enzymes for ergosterol biosynthesis, and this direct action is thought to underlie antifungal actions of these drugs. Recent studies showed that azoles alter expression of genes for various cellular functions. However, transcription factors regulated by azoles and their roles in antifungal actions remain poorly characterized. Using luciferase assay, we found that miconazole increased luciferase activity under the promoter containing the cAMP response element (CRE) motif. This azole-induced activation of CRE reporter was abolished in Atf1-deficient cells, suggesting that azoles induce Atf1 activation. As Atf1 is activated by stress-activated MAP kinase Sty1 upon various stressors, we examined its involvement. Azoles increased phosphorylation of Sty1 for its activation, and Sty1 deletion impaired azole-induced CRE reporter activation. In contrast, deletion of Pyp1, a tyrosine phosphatase which negatively regulates Sty1, increased CRE reporter activation. In addition, cells deficient in Atf1 and stress-activated MAP kinase pathway showed resistance to azoles, whereas cells lacking Pyp1 increased azole susceptibility, suggesting a critical role for azole-induced activation of MAP kinase-Atf1 pathway in antifungal actions of azoles. Collectively, these results suggest that azoles activate stress-activated MAP kinase pathway, thereby facilitating Atf1-mediated transcription for antifungal effects.

The security of engineering Saccharomyces cerevisiae is becoming more focused on industrial production in consideration of the public concern regarding genetically modified organisms. In this work, a rapid and highly efficient system for seamless gene deletion in S. cerevisiae was developed through two-step integration protocol combined with endonuclease I-SCEI expression. The factors affecting the frequency of the second homologous recombination were optimized, and studies indicated that the mutant strains with 500 bp direct repeats and that have been incubating in galactose (0.5 g/100 mL) medium at 30°C and 180 r/min for 24 h permit high frequency (6.86 × 10^-4) of the second homologous recombination. Furthermore, DNA sequence assays showed only self-DNA in native location without any foreign genes after deletion using this method. The seamless gene deletion method was applied to the construction of the engineering strains with BAT2 (encoding aminotransferase) deletion and ATF1 (alcohol acetyltransferases) overexpression. The mutants exhibited significant effects on higher alcohol reduction and ester improvement after Baijiu fermentation. The engineered strains can be used in industrial production in security, thereby meeting the requirements of modern science and technology.

The human TSC2 gene, mutations in which predispose individuals to the disease tuberous sclerosis complex (TSC), encodes a GTPase-activating protein for the GTPase RHEB. Loss of TSC2 results in constitutive activation of RHEB and its target mammalian target of rapamycin (mTOR). We have previously reported that fission yeast (Schizosaccharomyces pombe) Tf2 retrotransposons (hereafter Tf2s) are abnormally induced upon nitrogen starvation in cells lacking the tsc2+ gene (Δtsc2), a homolog of the human TSC2 gene, and in cells with a dominant-active mutation in the fission yeast RHEB GTPase (rhb1-DA4). We report here that induction of Tf2s in these mutants is suppressed upon overexpression of the cgs2+ gene, which encodes a cAMP-specific phosphodiesterase, or upon deletion of components in the glucose/cAMP signaling pathway, namely Cyr1, Pka1, Tor1 and the stress-activated transcription factor Atf1. The results suggest that the glucose/cAMP signaling pathway is downregulated when cells are starved for nitrogen. We also show that Tf2 proteins are degraded via autophagy, which is under control of Tor2, a homolog of human mTOR. It appears that failure in the two processes, downregulation of the glucose/cAMP signaling pathway and induction of autophagy, allows abnormal induction of Tf2s upon nitrogen starvation in Δtsc2 and rhb1-DA4 cells.

Gene expression from the new embryonic genome is required for normal preimplantation embryo development. Two members of the cAMP-responsive element-binding protein (Creb) family of transcription factors, Creb1 and activating transcription factor 1 (Atf1), are essential for normal preimplantation development. These transcription factors are activated by phosphorylation. Creb1 mRNA was expressed throughout the preimplantation phase. Cytoplasmic immunolocalization of Creb1 was detected in all preimplantation embryo stages. The antigen was largely excluded from the pronuclei/nuclei at embryonic stages except in the mid-cycle two-cell and compacted eight-cell embryo. Activation-state-specific antibodies showed serine 133 phosphorylated Creb1 localization was similar to Creb1 staining, except that there was no increase in staining at the eight-cell stage. Increased staining of phosphorylated Creb1 was observed in the nucleus of mid-cycle two-cell embryos. Increased expression of phosphorylated Creb1 in the two-cell embryo was induced by brief exposure of embryos to ionomycin, but not by a dibutyryl cAMP. This was blocked by buffering intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester), but not by a cAMP antagonist, Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine. Calmodulin is an intracellular receptor for calcium. Calmodulin mRNA was expressed throughout the preimplantation phase of development. The calmodulin antagonist, W-7, inhibited the ionomycin-induced localization of phosphorylated Creb1 in the nucleus. Treatment of embryos with W-7 caused a dose-dependent inhibition of normal development of zygotes to the blastocysts stage. The study shows Creb1 expression and nuclear localization was dynamically regulated in the early embryo. The marked nuclear accumulation and phosphorylation of Creb1 at the two-cell stage occurred at the time of transcription from the embryonic genome and was regulated in a calcium- and calmodulin-dependent manner.

Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.

Nitric Oxide (NO) and its associated reactive nitrogen species (RNS) produce nitrosative stress under various pathophysiological conditions in eukaryotes. The fission yeast Schizosaccharomyces pombe regulates stress response mainly through the Sty1-Atf1 MAP Kinase pathway. The present study deals with the role of transcription factor Atf1 and Sty1 in S. pombe under nitrosative stress. In this study, exposure to an NO donor resulted in S-phase slowdown with associated mitotic block in S. pombe. Deletion of sty1 and atf1 in S. pombe had differential growth sensitivity towards NO donor. Both Sty1 and Atf1 were involved in regulating mitotic slowdown in S. pombe under nitrosative stress. Experimental data obtained in this study reveals a novel role of Atf1 in initiating the replication slowdown in S. pombe under nitrosative stress. Both Sty1 and Atf1 were accumulated in the nucleus in S. pombe under nitrosative stress in a concentration and time dependent manner. Atf1 is also found to be nuclear delocalized under longer nitrosative stress.

A variety of soft tissue and visceral neoplasms have been associated with constitutional symptoms and signs including fever, fatigue, arthritis and laboratory abnormalities such as elevated erythrocyte sedimentation rate, leukocytosis with marked neutrophilia, anemia, thrombocytosis and others. This review addresses three main neoplastic categories that are associated with specific paraneoplastic phenomena: (1) neoplasms having in common the presence of diffuse mixed inflammatory infiltration (closely simulating an inflammatory pseudotumor) and frequently associated with constitutional symptoms; (2) neoplasms with undifferentiated, anaplastic or rhabdoid cell morphology (frequently SWI/SNF-deficient) associated with diverse paraneoplastic manifestations; and (3) paraneoplasia associated with neoplasms carrying specific gene fusions such as solitary fibrous tumor (STAT6-NAB2 gene fusions), infantile fibrosarcoma and congenital mesoblastic nephroma (ETV6-NTRK3 gene fusions), and angiomatoid fibrous histiocytoma (EWSR1-CREB1 & EWSR1-ATF1 fusions).

The presence of melanocytic differentiation in tumors of non-melanocyte origin is uncommon and is typically associated with the overexpression of MITF, the master regulator of melanin synthesis, or another member of the MIT/TFE3 family. In clear cell sarcoma, the presence of either an EWSR1-ATF1 or EWSR1-CREB1 translocation-derived fusion protein is thought to drive melanocytic differentiation by directly stimulating the expression of MITF. Here, we describe a clear cell neoplasm with melanocytic differentiation that is characterized by a novel MITF-CREM gene fusion. CREM is the third member of the ATF1/CREB1/CREM family, and the nature of the MITF-CREM fusion appears analogous to the EWSR1-ATF1 and EWSR1-CREB1 fusions. Thus, this MITF-CREM-rearranged clear cell tumor represents a novel entity with morphologic, immunohistochemical, and molecular similarity to clear cell sarcoma.

Keywords: CREM; Clear cell sarcoma; MITF; Melanocytic; Translocation.

Activating transcription factor 1 (ATF1), belonging to the CREB/ATF family of transcription factors, is highly expressed in the testes. However, its role in spermatogenesis has not yet been established. Here, we aimed to elucidate the impact of ATF1 in spermatogenesis by examining the expression pattern of ATF1 in mice and the effect of ATF1 knockdown in the mouse testes. We found that ATF1 is expressed in various organs, with very high levels in the testes. Immunohistochemical staining showed that ATF1 was localized in the nuclei of spermatogonia and co-localized with proliferating cell nuclear antigen. In ATF1-deficient mice, the seminiferous tubules of the testis contained cells at all developmental stages; however, the number of spermatocytes was decreased. Proliferating cell nuclear antigen expression was decreased and apoptotic cells were rare in the seminiferous tubules. These results indicate that ATF1 plays a role in male germ cell proliferation and sperm production.

Keywords: ATF1; proliferation; spermatogenesis; spermatogonia.

To understand the individual enological function of different unsaturated fatty acids (UFAs), the separated effects of three different UFAs, linoleic acid (LA), oleic acid (OA), and α-linolenic acid (ALA), on yeast fermentation and aroma compounds were investigated in the alcoholic fermentation of Cabernet Sauvignon wine. The results showed that, besides concentration, UFAs types could also influence fermentation process and volatiles in final wine. Low concentrations of UFAs (12 and 60 mg/L), especially LA and OA, significantly promoted fermentation activity and most volatiles when compared to the control, however, the effect became the inhibition with increasing concentrations of UFAs (120 and 240 mg/L). It was interesting to find that OA addition (12 and 60 mg/L) could generate more acetate esters (especially isoamyl acetate) in wine, while 12 mg/L LA facilitated more fatty acids formation (octanoic acid and decanoic acid). In comparison, 120 and 240 mg/L ALA produced more amount of C6 alcohols (1-hexanol) and higher alcohols (isobutyl alcohol and 2,3-butanediol). UFAs additions were unfavorable for ethyl esters formation, except for an increment of ethyl hexanoate in 12 mg/L OA wine. As a result, different aromatic profiles of wines were generated by variations of UFAs types and levels, as shown by PCA. The transcriptional data revealed that the expressions of aroma-related genes, such as BAT1, BAT2, PDC1, PDC5, PDC6, ACC1, FAS1, ATF1, EEB1, and EHT1 were correlated with aroma compounds productions in different treatments. Our data suggested that the three UFAs have different enological functions and they could generate different aromatic profiles. Thus, besides concentrations, it is essential to consider the types of UFAs when applying the strategy to adjust UFAs contents to modulate the aromatic quality of wines.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Clear cell sarcoma of tendons and aponeuroses (CCS) is an uncommon malignancy characterized by a t(12;22)(q13;q12) causing a fusion of the EWS and ATF1 genes. We describe the cytogenetic and molecular genetic analyses of two lung metastases from a CCS patient. Both lesions presented the defining t(12;22) and a type 1 EWS/ATF1 chimeric transcript. The additional cytogenetic changes present in the two lesions allowed us to obtain some insight into the pathogenetic basis of disease progression. Four related clones were identified in the right lung metastasis, permitting a partial reconstitution of the stepwise clonal evolution, whereas the left lung metastasis presented yet another subclone. The comparison of the two karyotypes enabled us to pinpoint which changes occurred in the primary tumor and which emerged independently after the two metastases had been established. We conclude that both clonal divergence and convergence may be operative during tumor progression of CCS.

Clear cell sarcoma (CCS) of tendons and aponeuroses is an aggressive neoplasm that is characterized by a pathognomonic translocation, t(12;22)(q13;q12), resulting in an EWSR1-ATF1 chimeric gene. We report for the first time a female patient with CCS exhibiting both EWSR1-ATF1 fusion transcripts and hereditary homozygous point mutations in introns 11 and 16 of the KIT gene. Her parents and two brothers each had heterozygous point mutations in intron 11 or intron 16 of the KIT gene. The functional significance of these germline deep intronic point mutations and their relationship to the pathogenesis of CCS are unclear. Future studies investigating KIT intron mutations in a larger cohort of CCS patients are warranted.

BACKGROUND

Clear cell melanoma is a recently described variant of melanoma characterized by prominent clear cell features similar to clear cell sarcoma.

METHODS

The present report describes a deeply invasive case of clear cell melanoma clinically, histologically, immunohistochemically, ultrastructurally and with the FISH technique and compares these findings with those in clear cell sarcoma.

RESULTS

A 68-year-old male presented with an ulcerated, deeply invasive melanoma on the heel, corresponding to Clark level V, with a maximum tumour thickness of more than 14 mm; follow-up revealed inguinal lymph-node and lung metastases. Apart from characteristic histological features of melanoma with intraepidermal involvement, the lesion was immunohistochemically positive for 5100 protein, with HMB45 and A103 (anti-human Melan-A/MART-1), and ultrastructurally showed melanosomes. In deeply invasive parts, the lesion was indistinguishable from clear cell sarcoma, exhibiting nests, fascicles and sheets of pale-staining epithelioid to spindle-shaped cells ('clear cells') with scattered Touton-like multinucleated giant cells. Cytogenetic analysis using the FISH technique revealed a 12q13 chromosomal break in the vicinity of the ATFI gene but without ATF1 disruption.

CONCLUSIONS

These findings may indicate the possible involvement of the ATF1 gene in clear cell melanoma tumorigenesis, similar to clear cell sarcoma with classical t(12;22) translocation.

Clear cell sarcoma (CCS) of tendons and aponeuroses, also known as melanoma of soft parts, represents an aggressive rare malignancy that is characterized by a nested or fascicular pattern of spindled cells and a pathognomonic reciprocal translocation, t(12;22)(q13;q12), that results in the fusion of EWSR1 and ATF1 genes. Numerous recent studies have recognized the importance of a cutaneous CCS variant that can mimic a broad spectrum of entities, including spindle cell melanoma, spindle cell squamous carcinoma, cutaneous leiomyosarcoma and atypical fibroxanthoma. We report a case of a 13-year-old boy with cutaneous CCS who presented with a few months history of an asymptomatic papule on the lower lip that was suggestive of a mucocele. Biopsy of the lesion showed a wedge shaped neoplasm arranged in nests and fascicles of epithelioid- to oval-shaped cells with pale cytoplasm, open chromatin and prominent nucleolus. The superficial component was closely opposed to the basal epithelium resembling the junctional nests of a melanocytic neoplasm. The process extended into and involved the striated muscle of the lip. The cells expressed S-100, CD99 and synaptophysin by immunohistochemistry, and there was focal HMB-45 and microphthalmia transcription factor (MiTF) positivity as well. Fluorescence in situ hybridization confirmed the presence of the t(12;22) (ESWR1-ATF1) translocation.

Clear cell sarcoma (CCS) is a rare, low-grade carcinoma commonly located in the distal extremities of young adults involving tendons and aponeuroses. CCS is characterized by its poor prognosis due to late diagnosis, multiple local recurrence, propensity to late metastases, and a high rate of tumor-related mortality. The genetic cause for CCS is thought to be EWSR1 gene translocation. However, CCS lacking a translocation may have other, as yet uncharacterized, genetic mutations that can cause the same pathological effect. A combination of whole‑exome sequencing and Sanger sequencing of cancer tissue and venous blood from a patient diagnosed with CCS of the salivary gland revealed a somatic missense mutation, c.1061C>T (p.P354L), in exon 9 of the Nibrin gene (NBN). This somatic missense mutation led to the conversion of proline to leucine (p.P354L), resulting in deleterious effects for the NBN protein. Multiple-sequence alignments showed that codon 354, where the mutation (c.1061C>T) occurs, is located within a phylogenetically conserved region. In conclusion, we here report a somatic missense mutation c.1061C>T (p.P354L) in the NBN gene in a patient with CCS lacking an EWSR1-ATF1 fusion. Our findings broaden the genotypic spectrum of CCS and provide new molecular insight that should prove useful in the future clinical genetic diagnosis of CCS.

The cellular oncoprotein Ewing's sarcoma oncogene (EWS)/activating transcription factor 1 (ATF1) is a highly specific marker for malignant melanoma of soft parts (MMSP) and is a potent activator of several cAMP-inducible promoters, including the somatostatin promoter. Here we explored the potential for using the somatostatin promoter to direct toxic gene expression in MMSP cells. When introduced into MMSP cells, a somatostatin-herpes simplex virus thymidine kinase fusion gene confers strong and cell-specific sensitivity to the cytotoxic prodrug ganciclovir. Ganciclovir sensitivity requires the ATF-binding site present in the somatostatin promoter, indicating that toxic gene expression is caused by EWS/ATF1. We also tested the efficacy of recombinant adenoviruses adenoviruses for gene delivery and expression in two MMSP cell lines (DTC1 and Su-ccs-1). Surprisingly, several promoters (including somatostatin) that are strongly activated by EWS/ATF1 in transient assays are not activated in DTC1 and Su-ccs-1 cells when present in an adenovirus vector. In summary, our findings demonstrate the potential for using the somatostatin promoter for cytotoxic prodrug therapy for MMSP. However, first-generation adenovirus vectors cannot be used as promoter delivery vehicles for toxic gene expression in MMSP cells.

Antibody variable domains represent potential structural models for the rational design of therapeutic molecules that bind cellular proteins with high affinity and specificity. The Activating Transcription Factor 1 (ATF1)/Cyclic AMP Response Element Binding Protein (CREB) family of transcription factors are particularly relevant targets due to their strong association with melanoma and clear cell sarcoma. Biochemical and structural investigations were performed to optimize a single-chain antibody fragment (scFv), scFv41.4, that disrupts the binding of ATF1/CREB to cyclic-AMP response elements (CRE) in vitro and inhibits transcriptional activation in cells. Molecular modeling and ligand docking simulations suggested that scFv41.4 could function as a disulfide-deficient single domain scFv. Functional studies verified that deletion of the light chain did not result in reduced inhibitory activity. The isolated heavy chain was predicted to assume a relaxed structural conformation that maintained a functional antigen binding pocket. The minimal structural elements necessary for intracellular function were further analyzed by selective deletion of CDR1 and CDR2. V(H)-CDR1 and V(H)-CDR3 were shown to play a key role in antigen binding activity, but V(H)-CDR2 was dispensable. Thus, scFv41.4 represents a unique molecule with potential for use in the design of peptidomimetic derivatives having therapeutic application to human cancer.

Malignant neoplasms very rarely metastasize to the mammary gland, the incidence of which is reported as 0.5-2%. Clear cell sarcoma is a rare neoplasm, accounting for approximately 1% of all soft tissue tumors, which commonly occurs in the distal extremities of young adults aged approximately 20 to 40 years. So it is also called malignant melanoma of soft parts because it frequently produces melanin. We report a case of a 26-year-old woman who presented with a neck mass. The mass was surgically removed, and pathological diagnosis was clear cell sarcoma of the neck, harboring the EWS-ATF1 chimeric gene. Computed tomography detected a right breast mass 11 months after operation. She was referred to our department, and the right breast tumor was resected. Histopathological examination revealed a 2.5-cm, well-defined mass composed of nests of small, spindle-shaped tumor cells with abundant, clear cytoplasm containing round nuclei and prominent nucleoli. The tumor cells were immunohistochemically positive for HMB45, S-100, and Melan-A. These findings led to a diagnosis of metastasis of clear cell sarcoma to the mammary gland. This is the first report of clear cell sarcoma of the neck which metastasized to the mammary gland.

UNASSIGNED

Lactucopicrin is one of constitutes in Cichorium intybus L, which is commonly known as chicory in worldwide. It has been used for traditional usage such as antianalgesics, antidepressants and antihyperglycemics AIM OF STUDY: We investigated the neurotrophin-mediated neuroprotective effect of lactucopicrin in in vitro and examined for the underlying mechanism.

METHODS

To verify the neuroprotective effect of lactucopicrin, we investigated the inhibitory AChE activity, neurite outgrowth-related downstream signaling in murine neuroblastoma N2a and neurotrophins secretion in rat C6 glioma cells.

RESULTS

Lactucopicrin inhibited the AChE activity and increased intracellular Ca2+ levels with a substantial rise in muscarinic acetylcholine receptor M1 (CHRM1) expression in N2a cells. Moreover, lactucopicrin actively promoted neurite outgrowth via Ca2+-mediated activation of Ca2+/calmodulin-dependent protein kinase-II (CaMKII). It further activates transcription factor 1 (ATF1) along with modulating the levels of tropomyosin receptor kinase A, extracellular signal-regulated kinase 1 and 2, AKT, and synaptophysin 1 in N2a cells. Additionally, the levels of neurotrophins including NGF, BDNF, and NT3 were increased by treatment of lactucopicrin in C6 cells. The effects of lactucopicrin on NGF secretion and neuritogenesis were maintained even in the presence of phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002, indicating that lactucopicrin exerts its effect on neuritogenesis in a PI3K-independent manner.

CONCLUSIONS

Our results suggest that the natural compound lactucopicrin may be a promising neurotrophin-mediated neuroprotective candidate for neurodegenerative diseases.

Lung cancer is among the most frequently occurring cancers and the leading cause of cancer-related deaths worldwide. Nonsmall cell lung cancer is accountable for 85% to 90% of all lung cancer cases and develops distant metastases with high mortality. In this work, we elucidated the role of activating transcription factor 1 (ATF1) in migration and invasion of lung cancer cells. We found that the migration and invasion were inhibited with ATF1 silencing in lung cancer cells. By contrast, ATF1 overexpression led to promotion in migration and invasion. The alteration in ATF1 expression induced a change in the epidermal growth factor receptor (EGFR) and matrix metalloproteinases (MMP)-2 expression level in the same tendency. Thus, we provided a potential new candidate for therapies against lung cancer, showing the possible mechanism underlying the invasion and migration of lung cancer cells.