Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next‐generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up‐regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC‐1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.     

Uridine phosphorylase 1 associates to biological and clinical significance in thyroid carcinoma cell lines

Thyroid cancer incidence has been continuity increasing worldwide. Uridine phosphorylase 1 (UPP1) is a protein‐coding gene and has been detected that UPP1 was the higher expression in many solid malignancies, just as head and neck cancers, breast cancer, compared with paired normal tissue. But the act of UPP1 in thyroid cancer is not explicit. In this article, we investigate the function of UPP1 expression in thyroid cancer. The Cancer Genome Atlas (TCGA) unpaired thyroid cancer and normal RNA‐seq data were downloaded, and our paired thyroid cancer and normal samples were analysed by a polymerase chain reaction. The expression of UPP1 was regulated by transfected small interfering RNA, and the function of UPP1 was determined via migration, invasion and cell proliferation assays. Western blot assay was achieved to determine the UPP1 expression correlates with the function of 5‐FU regulate epithelial‐mesenchymal transition. The significant upregulation of UPP1 in thyroid cancer tissues compared with normal thyroid tissues was revealed by our data and TCGA data. UPP1 overexpression was significantly correlated with lymph node metastasis, tumour stage and tumour size. In the cell, experiments showed that UPP1 low expression significantly suppressed the migration, invasion and proliferation. Western blot assay proves the effect of UPP1 expression on 5‐FU regulates epithelial‐mesenchymal transition pathway. UPP1 plays a crucial oncogene in thyroid cancer. Our findings indicate that UPP1 might be a biomarker of thyroid cancer and may act by regulating epithelial‐mesenchymal transition (EMT).     

HORMAD2 methylation‐mediated epigenetic regulation of gene expression in thyroid cancer

This study is aimed to investigate the methylation level of candidate genes and its impact on thyroid carcinoma (THCA) development. Infinium Human Methylation 450 BeadChip Arrays by Illumina (Illumina HM450K) was the most popular CpG microarray platform widely used in biological and medical research. The methylation level of differentially expressed genes and their corresponding CpG sites were analysed by R programme. The expression of HORMAD2 was evaluated by qRT‐PCR and Western blot, while the methylation level was examined via methylation‐specific PCR. Cell viability, metastasis, cell cycle and apoptosis were detected by MTT assay, transwell and wound healing assay and flow cytometry, respectively, after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza). Tumour formation assay was used to analyse thyroid tumour growth in nude mice in vivo. The methylation levels of all 116 differentially expressed genes were analysed. HORMAD2 was significantly hypermethylated and its mRNA expression was inhibited in THCA cells. After treatment with 5‐Aza, HORMAD2 expression was up‐regulated in THCA cells and its overexpression can suppress thyroid cancer cell viability, mobility and invasiveness remarkably. Up‐regulation of HORMAD2 in THCA cells could prolong G0/G1 phase and shorten S phase to impede cell mitosis as well as promote thyroid cancer cells apoptosis. Furthermore, tumour formation assay showed that increased HORMAD2 level impeded tumour growth in vivo. Hypermethylation of HORMAD2 could induce THCA progression, while hypomethylation of HORMAD2 retard cell growth and mobility and facilitate apoptosis through increasing its mRNA expression.     

Long noncoding RNA LINC00978 promotes cancer growth and acts as a diagnostic biomarker in gastric cancer

Objectives

Long noncoding RNAs (lncRNAs) play important roles in cancer development and progression. The deregulated expression of LINC00978 has been reported in human cancers. However, the expression pattern and biological roles of LINC00978 in gastric cancer (GC) remain unclear. In this study, we investigated the potential roles and clinical value of LINC00978 in gastric cancer.

Materials and methods

QRT‐PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines, tissues and serum samples. Cell counting, colony formation, transwell migration and matrigel invasion assays were performed to determine the effects of shRNA‐mediated knockdown of LINC00978 on gastric cancer cell functions. In vivo tumour growth assay was also conducted. Flow cytometry, immunohistochemistry, western blot and qRT‐PCR were used for potential mechanism study.

Results

LINC00978 expression level was elevated in GC tumour tissues, serum samples and cell lines. The expression level of LINC00978 was significantly correlated with tumour size (P = 0.02), lymphatic metastasis (P = 0.009) and TNM stage (P = 0.009). LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis. LINC00978 knockdown also inhibited the migration and invasion of GC cells. In addition, LINC00978 knockdown inhibited the activation of TGF‐β/SMAD signalling pathway and the process of epithelial‐mesenchymal transition (EMT) in GC cells. Moreover, the in vivo tumorigenicity of LINC00978 knockdown GC cells in mice was significantly decreased.

Conclusions

LINC00978 promotes gastric cancer progression and may serve as a potential biomarker for GC.     

Influence of type‐I Interferon receptor expression level on the response to type‐I Interferons in human pancreatic cancer cells

Pancreatic cancer is a highly aggressive malignancy with limited treatment options. Type‐I interferons (e.g. IFN‐α/‐β) have several anti‐tumour activities. Over the past few years, clinical studies evaluating the effect of adjuvant IFN‐α therapy in pancreatic cancer yielded equivocal results. Although IFN‐α and ‐β act via the type‐I IFN receptor, the role of the number of receptors present on tumour cells is still unknown. Therefore, this study associated, for the first time, in a large panel of pancreatic cancer cell lines the effects of IFN‐α/‐β with the expression of type‐I IFN receptors. The anti‐tumour effects of IFN‐α or IFN‐β on cell proliferation and apoptosis were evaluated in 11 human pancreatic cell lines. Type‐I IFN receptor expression was determined on both the mRNA and protein level. After 7 days of incubation, IFN‐α significantly reduced cell growth in eight cell lines by 5–67%. IFN‐β inhibited cell growth statistically significant in all cell lines by 43–100%. After 3 days of treatment, IFN‐β induced significantly more apoptosis than IFN‐α. The cell lines variably expressed the type‐I IFN receptor. The maximal inhibitory effect of IFN‐α was positively correlated with the IFNAR‐1 mRNA (P < 0.05, r = 0.63), IFNAR‐2c mRNA (P < 0.05, r = 0.69) and protein expression (P < 0.05, r = 0.65). Human pancreatic cancer cell lines variably respond to IFN‐α and ‐β. The expression level of the type‐I IFN receptor is of predictive value for the direct anti‐tumour effects of IFN‐α treatment. More importantly, IFN‐β induces anti‐tumour effects already at much lower concentrations, is less dependent on interferon receptor expression and seems, therefore, more promising than IFN‐α.     

LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple‐negative breast cancer (TNBC) patients. The ratio and mammosphere‐forming ability of CD44+/CD24? stem‐like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag‐based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44⁺/CD24^? stem‐like cells and their mammosphere‐forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation‐related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial‐mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH‐silenced cells and LIPH‐mediated modulation of tumour cell adhesion depended on integrin‐related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up‐regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.     

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.     

Reduced expression of proteolipid protein 2 increases ER stress-induced apoptosis and autophagy in glioblastoma

Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high-grade gliomas than in low-grade gliomas. We confirmed these results at the protein level through IHC staining of high-grade (n = 56) and low-grade glioma biopsies (n = 16). Kaplan-Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87- and U251-siPLP2 cells. Finally, intracranial xenografts derived from U87- and U251-shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.     

Protein kinase D1 regulates ERα‐positive breast cancer cell growth response to 17β‐estradiol and contributes to poor prognosis in patients

About 70% of human breast cancers express and are dependent for growth on estrogen receptor α (ERα), and therefore are sensitive to antiestrogen therapies. However, progression to an advanced, more aggressive phenotype is associated with acquisition of resistance to antiestrogens and/or invasive potential. In this study, we highlight the role of the serine/threonine‐protein kinase D1 (PKD1) in ERα‐positive breast cancers. Growth of ERα‐positive MCF‐7 and MDA‐MB‐415 human breast cancer cells was assayed in adherent or anchorage‐independent conditions in cells overexpressing or depleted for PKD1. PKD1 induces cell growth through both an ERα‐dependent manner, by increasing ERα expression and cell sensitivity to 17β‐estradiol, and an ERα‐independent manner, by reducing cell dependence to estrogens and conferring partial resistance to antiestrogen ICI 182,780. PKD1 knockdown in MDA‐MB‐415 cells strongly reduced estrogen‐dependent and independent invasion. Quantification of PKD1 mRNA levels in 38 cancerous and non‐cancerous breast cell lines and in 152 ERα‐positive breast tumours from patients treated with adjuvant tamoxifen showed an association between PKD1 and ERα expression in 76.3% (29/38) of the breast cell lines tested and a strong correlation between PKD1 expression and invasiveness (P < 0.0001). In tamoxifen‐treated patients, tumours with high PKD1 mRNA levels (n = 77, 50.66%) were significantly associated with less metastasis‐free survival than tumours with low PKD1 mRNA expression (n = 75, 49.34%; P = 0.031). Moreover, PKD1 mRNA levels are strongly positively associated with EGFR and vimentin levels (P < 0.0000001). Thus, our study defines PKD1 as a novel attractive prognostic factor and a potential therapeutic target in breast cancer.     

17‐AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway

The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17‐Allylamino‐17‐ demethoxygeldanamycin (17‐AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes‐associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17‐AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P < 0.001), while that of YAP was elevated (76.0% versus 56.0%, P = 0.03) in LAC tissues compared to the adjacent non‐cancerous tissues; LAST1 expression was negatively correlated with YAP expression (r = 0.432, P < 0.001) and lymphatic invasion of the tumour (P = 0.015). In addition, 17‐AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E‐cadherin and p‐LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17‐AAG‐treated groups than those in untreated group (P < 0.01). Taken together, our findings indicate that decreased expression of LATS1 is associated with lymphatic invasion of LAC, and 17‐AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.     

Expression of Cripto‐1 predicts poor prognosis in stage I non‐small cell lung cancer

Cripto‐1 (CR‐1) is related to the biological behaviour and prognosis of carcinomas. The purpose of this study was to investigate the significance of CR‐1 expression in surgically resected stage I non‐small cell lung cancer (NSCLC). One hundred and forty‐eight patients with completely resected stage I NSCLC and available clinical follow‐up data were assessed. The protein expression of CR‐1 in the tumours was detected by immunohistochemistry. CR‐1 was highly expressed in 64 of 148 tumours. Among patients with high CR‐1 expression, progression‐free survival and overall survival rate were significantly lower than those of patients with low CR‐1 levels (P = .013 and P = .019, respectively). The incidence of distant metastasis in patients with high CR‐1 expression was significantly higher than that of in patients with low CR‐1 expression (57.13% vs 21.43%, P = .001). The results of the multivariate analysis confirmed that a high CR‐1 was a significant factor for poor prognosis. In conclusion, CR‐1 could be a useful prognostic factor in patients with stage I NSCLC, likely as an indicator of the metastatic propensity of the tumour.     

Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence

This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non‐destructive and operator‐independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods. A total of 136 patients were recruited. FTIR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were studied with transmittance FTIR spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode (ATR) of FTIR spectroscopy by a different operator. The results revealed significant alterations in moleculer content in the cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Similar results were also obtained by ATR‐FTIR spectroscopy. This study shows the power of infrared spectroscopy in the diagnosis of bladder cancer.

     

Clinical implications of activated leukocyte cell adhesion molecule expression in breast cancer

In the study, we enrolled 150 breast cancer cases to investigate the expression status of activated leukocyte cell adhesion molecule (ALCAM), and the relationships between ALCAM expression and clinical-pathological characteristics and prognosis of breast cancer. It was observed that ALCAM was expressed at higher levels in breast cancer tissue compared to levels observed for tumor-adjacent tissue. Compared to cancers with low membranous ALCAM expression, cancers with high membranous ALCAM expression were prone to lymph node metastasis (χ² = 15.910, P = 0.010) and metastasis in general (χ² = 5.211, P = 0.029). High cytoplasmic ALCAM expression was noticeably correlated with local recurrence (χ² = 7.379, P = 0.012), especially for short-term recurrence (interval <2 years) (χ² = 5.562, P = 0.037), while not associated to long-term local recurrence (interval >2 years). The content of ALCAM protein is closely associated with the expression of estrogen receptor (ER) (P = 0.024). The disease-free survival of patients with high cytoplasmic ALCAM expression was significantly shorter compared to the cases with low cytoplasmic ALCAM expression (P = 0.036). In conclusion, ALCAM expressed at high levels in breast cancer. High membranous expression of ALCAM probably resulted in weakened adherent ability and metastasis. In addition, high cytoplasmic ALCAM expression strengthened invasive ability of malignant cells and then promoted tumor development.     

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non‐coding RNA OTUB1‐isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1‐isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1‐isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1‐isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1‐isoform2 served as an independent negative prognostic predictor for disease‐free survival (DFS) and disease‐specific survival (DSS). Overexpression of OTUB1‐isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1‐isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.     

KANK1对子宫内膜癌细胞增殖及迁移的影响

摘要 目的：研究KANK1在子宫内膜癌中的表达以及对子宫内膜癌细胞增殖及迁移的影响。方法：（1）TCGA数据库分析KANK1在子宫内膜癌中的表达和生存期分析。（2）采用实时荧光定量聚合酶链反应验证转染KANK1质粒的效果。采用Ishikawa和ECC1这两种子宫内膜癌细胞来探讨KANK1对子宫内膜癌的细胞周期和凋亡的影响。通过Western blot检测细胞周期相关蛋白的表达,以及流式细胞术检测细胞周期和凋亡水平。（3）通过Transwell小室实验和划痕实验检测细胞的侵袭和转移能力。结果：TCGA数据库分析发现KANK1在子宫内膜癌中低表达且与患者预后良好相关。过表达KANK1下调了Cyclin D1和Cyclin D2的蛋白水平,并将细胞周期阻滞在G1期。流式细胞术检测发现过表达KANK1组的细胞凋亡水平（Ishikawa：22.7%;ECC1：19.0%）比对照组（Ishikawa：18.1%;ECC1：15.3%）高,差异具有统计学意义。Transwell迁移和侵袭实验结果表明过表达KANK1组的子宫内膜癌细胞侵袭和转移能力减弱。结论：本研究证明了KANK1在子宫内膜癌中发挥抑癌作用。KANK1高表达与子宫内膜癌的预后良好成正相关。KANK1通过抑制癌细胞周期和促进肿瘤细胞凋亡发挥抑制子宫内膜癌增殖的作用。此外,KANK1抑制了子宫内膜癌的侵袭和转移。     

Expression of stromal derived factor-1 (SDF-1) and chemokine receptor (CXCR4) in bone metastasis of renal carcinoma

Renal cancer is a relatively common malignant carcinoma that metastasizes to bone. The chemokine stromal derived factor-1 (SDF-1) and its corresponding receptor CXCR4 have been shown to regulate organ-specific metastasis in other cancer types. Based on this observation, we predicted that the expressions of SDF-1 and CXCR4 play a role in renal carcinoma metastasis to bone. To investigate the expressions of SDF-1 and CXCR4, and to assess the correlation between SDF-1 and CXCR4 immunoreactivity in bone metastasis of renal carcinoma, we collected 10 in situ renal carcinoma samples and 30 bone metastasis samples. We analyzed SDF-1 and CXCR4 expression with immunohistochemical analysis on paraffin-embedded sections. Compared with primary renal carcinomas, the SDF-1 expression in bone metastases was significantly higher [80% (24/30) vs. 30% (3/10), P = 0.006]; the expression of CXCR4 was also higher [83.3% (25/30) vs. 40% (4/10), P = 0.014]. Pearson correlation analysis supports a positive correlation between SDF-1 and CXCR4 in bone metastasis of renal carcinoma. In addition, RT-PCR demonstrated that, as compared with in situ renal carcinoma tissues, SDF-1 expression was predominant in the bone metastasis samples (P = 0.001), while CXCR4 was overexpressed in the bone metastasis tissues (P = 0.028). Western blot analysis confirmed these trends. Our data suggest that the expression of SDF-1/CXCR4 is high in bone metastases and over-expression of SDF-1/CXCR4 may play important roles in the bone metastasis of renal carcinoma.     

Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF‐β signalling

Gastric cancer (GC) is the fourth most common malignancy in males and the fifth most common malignancy in females worldwide. DACH1 is frequently methylated in hepatic and colorectal cancer. To further understand the regulation and mechanism of DACH1 in GC, eight GC cell lines, eight cases of normal gastric mucosa, 98 cases of primary GC and 50 cases of adjacent non‐tumour tissues were examined. Methylation‐specific PCR, western blot, transwell assay and xenograft mice were used in this study. Loss of DACH1 expression correlated with promoter region methylation in GC cells, and re‐expression was induced by 5‐Aza‐2′‐deoxyazacytidine. DACH1 is methylated in 63.3% (62/98) of primary GC and 38% (19/50) of adjacent non‐tumour tissues, while no methylation was found in normal gastric mucosa. Methylation of DACH1 correlated with reduced expression of DACH1 (P < 0.01), late tumour stage (stage III/IV) (P < 0.01) and lymph node metastasis (P < 0.05). DACH1 expression inhibited epithelial–mesenchymal transition and metastasis by inhibiting transforming growth factor (TGF)‐β signalling and suppressed GC cell proliferation through inducing G2/M phase arrest. The tumour size is smaller in DACH1‐expressed BGC823 cell xenograft mice than in unexpressed group (P < 0.01). Restoration of DACH1 expression also sensitized GC cells to docetaxel. These studies suggest that DACH1 is frequently methylated in human GC and expression of DACH1 was controlled by promoter region methylation. DACH1 suppresses GC proliferation, invasion and metastasis by inhibiting TGF‐β signalling pathways both in vitro and in vivo. Epigenetic silencing DACH1 may induce GC cells' resistance to docetaxel.