Insights into the roles of hnRNP A2/B1 and AXL in non-small cell lung cancer

Qu, Xiaohan; Liu, Jinlu; Zhong, Xinwen; Li, Xi; Zhang, Qi-Gang

doi:10.3892/ol.2015.3457

Cited by 21 publications

(10 citation statements)

References 26 publications

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“…Overexpression of hnRNP A2/B1 in non-small cell lung cancer increased cell proliferation, while downregulation of hnRNP A2/B1 enhanced apoptosis of breast cancer cells. Importantly, hnRNP A2/B1 has been used as biomarker and prognostic indicator in non-small cell lung cancer ( 9 – 13 ). However, the role of hnRNP A2/B1 in cervical cancer has not been fully studied.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of hnRNP A2/B1 inhibits cell proliferation, invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway

et al. 2018

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Cervical cancer is currently one of the major threats to women's health. The overexpression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as the biomarker has been investigated in various cancers. In our previous study, we found that lobaplatin induced apoptosis and cell cycle arrest via downregulation of proteins including hnRNP A2/B1 in cervical cancer cells. However, the underlying relationship between hnRNP A2/B1 and cervical cancer remained largely unknown. hnRNP A2/B1 knock-down in HeLa and CaSki cells was performed by shRNA transfection. The expression of hnRNP A2/B1 was detected by western blot and Quantitative Real-time PCR. Cell proliferation, migration, invasion and the IC50 of lobaplatin and irinotecan were determined by MTT assay, Transwell assay, Plate colony formation assay and wound healing assay. Flow cytometry was perfomed to investigate cell apoptosis and the cell cycle. The expression of PI3K, AKT, p-AKT, p21, p27, caspase-3, cleaved caspase-3 were revealed by western blot. Nude mouse xenograft model was undertaken with HeLa cells and the xenograft tumor tissue samples were analyzed for the expression of PCNA and Ki-67 by immunohistochemistry and the cell morphology was evaluated by hematoxylin and eosin (H&E). Results revealed that hnRNP A2/B1 was successfully silenced in HeLa and CaSki cells. hnRNP A2/B1 knock-down significantly induced the suppression of proliferation, migration, invasion and also enhancement of apoptosis and reduced the IC50 of lobaplatin and irinotecan. The expression of p21, p27 and cleaved caspase-3 in shRNA group were significantly upregulated and the expression of p-AKT was reduced both in vitro and in vivo. The results of immunohistochemistry showed that PCNA and Ki-67 were significantly downregulated in vivo. The growth of nude mouse xenograft tumor was significantly reduced by hnRNP A2/B1 knock-down. Taken together, these data indicate that inhibition of hnRNP A2/B1 in cervical cancer cells can inhibit cell proliferation and invasion, induce cell-cycle arrestment and trigger apoptosis via PI3K/AKT signaling pathway. In addition, after silencing hnRNP A2/B1 can increase the sensitivity of cervical cancer cells to lobaplatin and irinotecan.

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Section: Introductionmentioning

confidence: 99%

Knockdown of hnRNP A2/B1 inhibits cell proliferation, invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway

et al. 2018

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“…hnRNP A2/B1 has several cellular functions including regulating gene expression at the transcriptional and translational level. hnRNP A2/B1 has been reported to be overexpressed in tumorigenesis, and may be a potential biomarker for early detection, particularly in lung cancer (43). To assess the risk of human liver cancer, the increased expression and cytoplasmic localization of hnRNP A2/B1 may be used as a diagnostic biomarker (20).…”

Section: Discussionmentioning

confidence: 99%

Effect of Derris�scandens extract on a human hepatocellular carcinoma cell line

et al. 2018

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The incidence rate of hepatocellular carcinoma (HCC) remains high in numerous countries, including Thailand. There are numerous different lines of HCC treatment; however, various side effects and the resistance of cancer cells during treatment remain issues. At present, traditionally used herb plants have been widely used as alternatives to cancer therapy. Derris scandens is a Thai traditional herb which is commonly found in Thailand and widely used as a traditional medicine for numerous different diseases. The cytotoxicity of D. scandens ethanolic extract on a HCC cell line (HCC-S102) was determined using an MTT assay. Following treatment with D. scandens ethanolic extract, the induction of apoptosis was determined by Annexin V and dead cell assays, and then confirmed by the upregulation of cleaved poly(ADP-ribose) polymerase. Furthermore, a proteomic approach was used in order to study protein alteration upon treatment with D. scandens ethanolic extract coupled with liquid chromatography-tandem mass spectrometry analysis for protein identification. The results suggested that D. scandens ethanolic extract resulted in cytotoxicity against HCC-S102 cells, as the half-maximal inhibitory concentration values were 36.0±1.0, 29.6±0.6, and 22.6±1.5 µg/ml at 24, 48 and 72 h, respectively. Apoptotic cells were induced following treatment with D. scandens. The comparative proteomic profiles of D. scandens ethanolic extract-treated and untreated cells revealed various protein targets for anticancer activity including heterogeneous nuclear ribonucleoprotein (hnRNP) K, hnRNP A2/B1, stomatin-like 2 and GAPDH. In the present study, the anticancer activity of D. scandens ethanolic extract was demonstrated to affect the cell proliferation of HCC-S102 via an apoptotic pathway. The alteration in these proteins provides a better understanding of the mechanism of action of D. scandens, which may be a promising anticancer agent for the treatment of patients with HCC in the future.

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“…High AXL expression was noted in a subset of lung adenocarcinoma (LAC) and high AXL was associated with increasing tumor grade as well as metastasis and predicted poorer survival in patients. 25,[27][28][29][30] Furthermore, treatment of patient-derived NSCLC tumors with high AXL in mice with a monoclonal antibody against active AXL demonstrated antitumor activity, indicating a potential causal role of AXL in NSCLC tumorigenesis. 31 Yang et al evaluated the therapeutic potential of the AXL/MET selective inhibitors, BGB324 and cabozantinib, in cell and mouse xenograft models of lung squamous cell carcinoma (SCC).…”

Section: Axl As An Oncogene In Nsclcmentioning

confidence: 99%

Targeting AXL in NSCLC

Zaman

Bivona

2021

LCTT

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State-of-the-art cancer precision medicine approaches involve targeted inactivation of chemically and immunologically addressable vulnerabilities that often yield impressive initial anti-tumor responses in patients. Nonetheless, these responses are overshadowed by therapy resistance that follows. AXL, a receptor tyrosine kinase with bona fide oncogenic capacity, has been associated with the emergence of resistance in an array of cancers with varying pathophysiology and cellular origins, including in non-small-cell lung cancers (NSCLCs). Here in this review, we summarize AXL biology during normal homeostasis, oncogenic development and therapy resistance with a focus on NSCLC. In the context of NSCLC therapy resistance, we delineate AXL’s role in mediating resistance to tyrosine kinase inhibitors (TKIs) deployed against epidermal growth factor receptor (EGFR) as well as other notable oncogenes and to chemotherapeutics. We also discuss the current understanding of AXL’s role in mediating cell-biological variables that function as important modifiers of therapy resistance such as epithelial to mesenchymal transition (EMT), the tumor microenvironment and tumor heterogeneity. We also catalog and discuss a set of effective pharmacologic tools that are emerging to strategically perturb AXL mediated resistance programs in NSCLC. Finally, we enumerate ongoing and future exciting precision medicine approaches targeting AXL as well as challenges in this regard. We highlight that a holistic understanding of AXL biology in NSCLC may allow us to predict and improve targeted therapeutic strategies, such as through polytherapy approaches, potentially against a broad spectrum of NSCLC sub-types to forestall tumor evolution and drug resistance.

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Insights into the roles of hnRNP A2/B1 and AXL in non-small cell lung cancer

Cited by 21 publications

References 26 publications

Knockdown of hnRNP A2/B1 inhibits cell proliferation, invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway

Knockdown of hnRNP A2/B1 inhibits cell proliferation, invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway

Effect of Derris�scandens extract on a human hepatocellular carcinoma cell line

Targeting AXL in NSCLC

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