HGF Increases Cisplatin Resistance via Down-Regulation of AIF in Lung Cancer Cells

Chen, Jin Tang; Huang, Kevin Chih-Yang; Chiang, Yung Yen; Chen, Wen Heng; Chiou, Shiow-Her; Chen, Chih Yi; Chow, Kuan Chih

doi:10.1165/rcmb.2007-0001oc

Cited by 49 publications

(82 citation statements)

References 18 publications

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“…However, using in situ hybridization could adequately locate the HPV infection in UCC, not in the neighboring tissues (6). Moreover, our results indicate that HPV infection correlated with ATAD3A levels as well as those of c-MET, IL-8 and Ki-67 as well as with FIGO stages, lymph node involvement and patients' survival, which corresponded well with our prior studies that expression of these genes might be orchestrated with one another to form a malicious cycle in favor of cancer progression (6,26,27). It is worth noting that, Chinese UCC patients had a higher tendency of overexpressing ATAD3A than the American patients.…”

Section: Discussionsupporting

confidence: 89%

Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Chen

Hung²,

Lin

et al. 2011

Int J Mol Med

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Abstract. Our aim was to determine the association of human papillomavirus (HPV) infection with the expression of ATPase family AAA domain containing 3A (ATAD3A), an anti-autophagy factor, in uterine cervical cancer (UCC). The HPV genotype was determined by an Easychip HPV blot assay. ATAD3A expression was determined by immunohistochemical staining. High-risk HPV (hrHPV) was detected in 184 (88.9%) of 207 UCC cases. ATAD3A expression was detected in 164 (79.2%) UCC cases. A significant correlation was found between ATAD3A expression and the presence of hrHPV (p<0.001), FIGO stage (p=0.014), lymph node involvement (p=0.001), c-MET expression (p<0.001), interleukin-8 (p=0.03) and patient survival (p=0.0016). Interestingly, silencing of E6/E7 expression decreased ATAD3A expression and cell survival. Moreover, knockdown of ATAD3A (ATAD3A kd ) expression or addition of resveratrol, increased cellular autophagy and apoptosis and reduced drug resistance. Resveratrol reduced ATAD3A expression, and increased abrasion of the mitochondrial outer membrane as well as numbers of autophagosomes, the phenomena that were frequently found in ATAD3A kd cells. In conclusion, our results show that HPV infection correlates with increased ATAD3A expression and drug resistance in UCC. Persistent HPV infection may stabilize ATAD3A expression to inhibit cell autophagy and apoptosis as well as to increase drug resistance. IntroductionUterine cervical cancer (UCC) is the most prevalent cancer, and the fifth leading cause of cancer-related deaths in Taiwanese women (1). High incidence and mortality of the disease was in part due to the conservative attitude toward the Papanicolaou smear, because even though the disease could be detected at the early stages the method was considered intrusive, and in part due to the high infection rate of human papillomavirus (HPV) among the diseased women (2). HPV infection is a potential etiologic cause for UCC development (3,4). Among 95 known HPV (5), genotypes 16, 18, 52 and 58 are categorized as high-risk and most frequently detected in Taiwanese UCC patients (6-9). Carcinogenicity of the high-risk HPV (hrHRV) is closely associated with E6 and E7 proteins, which can respectively inhibit activities of tumor suppressors, p53 and retinoblastoma protein (pRB), to interrupt cell growth regulation (10). Besides carcinogenesis, persistent HPV infection further correlates with tumor recurrence, cancer cell radiosensitivity and the resulting poor prognosis (11-13).Oncogene activation is also crucial for tumorigenesis and cancer progression; in particular, genes that are associated with disease advancement and, possibly, resistance to irradiation and anticancer chemotherapeutics. By using differential display, we have identified overexpression of dihydrodiol dehydrogenase (DDH) in non-small cell lung cancer (14). Using microarrays, we further found that DDH was overexpressed in cisplatin-resistant ovarian cancer cells (15). Clinically, patients with elevated DDH have a higher tumor recurrence rate and lymph node...

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Section: Discussionsupporting

confidence: 89%

Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Chen

Hung²,

Lin

et al. 2011

Int J Mol Med

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“…Eletrophoresis was carried out in two 10% polyacrylamide gels with 4.5% stacking. One gel was processed for immunoblotting (20)(21)(22)(23)(24)(25)(26), and the other gel was stained with Coomassie blue. After electrophoresis, proteins on the first gel were transferred to a nitrocellulose membrane for immunoblotting.…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemical staining was performed according to the immunoperoxidase method previously reported (20)(21)(22)(23)(24)(25)(26).…”

Section: Methodsmentioning

confidence: 99%

“…HGF was correlated with tumor stages and poor prognosis (25). Of note, HGF not only increased resistance to cisplatin, but also reduced levels of apoptosis inducing factor (AIF), a vital factor of caspase-independent cell death (CICD), in NSCLC (25,26). Reduced effect of EGFR tyrosine kinase inhibitor (TKI), gefitinib, in patients with smoking habits or amplified c-MET gene suggested that in addition to cisplatin HGF might be involved in resistance to TKI as well (27).…”

Section: Introductionmentioning

confidence: 99%

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Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

et al. 2013

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Abstract. Our previous study showed that patients with advanced stages of non-small cell lung cancer (NSCLC) were frequently detected with upregulation of hepatocyte growth factor (HGF). In vitro, HGF reduced expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in NSCLC cells. The effect of HGF was via HGF receptor (c-MET) and the downstream effector, focal adhesion kinase (FAK). In this study, we determined the prognostic value of AIF in NSCLC patients. AIF expression was determined by immunohistochemistry and immunoblotting. Our data show that AIF expression was associated with better prognosis. Expression of AIF inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix metalloproteinase (MMP)-1, and HER2/neu, which were closely associated with drug resistance, tumor recurrence, metastasis and poor prognosis. Noteworthy, silence of HER2/neu gene expression increases AIF level and drug sensitivity. Addition of HGF inhibits AIF expression in HER2/neu-silenced cells. These results suggested that both HGF and HER2/neu affect drug resistance by regulating AIF expression in NSCLC. IntroductionLung cancer is one of the leading causes of cancer death worldwide. In the United States, the annual mortality rate of lung cancer (estimated 180,000 deaths, male: 73.5/10 5 personyear; female: 41.5/10 5 person-year) is approximately 30% of total cancer-related deaths (1), and nearly 85-90% of lung cancer deaths are attributed to tobacco smoking (2). In Taiwan, the annual mortality rate of lung cancer is approximately 20% (estimated 6,000 deaths, male: 21/10 5 person-year; female: 10.3/10 5 person-year) (3). Lung carcinoma is categorized into small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) with neuroendocrine features of the cancer cells. Based on the histopathological characteristics, NSCLC can be subcategorized into adenocarcinoma (ADC), squamous cell carcinoma and large cell carcinoma (4). Of note, among these, ADC, which is associated with a higher frequency of drug resistance and mortality than the other types, is most commonly found in women and smokers (5).Previous studies have indicated that tobacco smoking is a key risk factor for lung cancer (1,2,5,6). In patients with stage I NSCLC, we demonstrated that tobacco smoking and tumor size, but not visceral pleural invasion, are major factors influencing overall and disease-free survival (6). Moreover, accumulated evidence showed that NSCLC patients who continued to smoke were more resistant to chemotherapy and irradiation, and had poorer prognosis (6-9). Although nicotine per se is not directly associated with tumorigenesis, catalyzed nicotine is carcinogenic (10,11). In addition, nicotine induces NSCLC growth, and increases angiogenesis in tumors probably via activating nicotinic acetylcholine receptor (nAchR), epidermal growth factor receptor (EGFR) and .Using differential display alone or in combination with microarray, we previously identifi...

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“…In this regard, some authors have pointed out that HGF protects tumor cells against the cytotoxicity and apoptosis induced by DNA-damaging agents, such as ionizing radiation or adriamycin (Shen et al, 2007), and that it may contribute to the resistance of RMS cells to conventional treatment (Jankowski et al, 2003). Similarly, it has been suggested that this factor could induce resistance to cisplatin in lung cancer cells (Chen et al, 2008). Nevertheless, in contrast to expectations, it has also been observed that HGF sensitizes ovary cancer cells to the drugs paclitaxel and cisplatin (Bardella et al, 2007).…”

Section: The Influence Of Growth Factors In the Sensitivity Of Tumor mentioning

confidence: 97%

Growth Factors and the Redox State as New Therapeutic Targets for Colorectal Cancer

Palomares¹,

Caramés²,

Garcı́a-Alonso³

et al. 2012

Colorectal Cancer Biology - From Genes to Tumor

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HGF Increases Cisplatin Resistance via Down-Regulation of AIF in Lung Cancer Cells

Cited by 49 publications

References 18 publications

Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

Growth Factors and the Redox State as New Therapeutic Targets for Colorectal Cancer

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