L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells

Yoon, Hyunho; Kim, Jung Min; Lee, Dong Gwang; Kim, Dae‐Ghon; Koh, Sang Seok; Hong, Hyo Jeong

doi:10.1016/j.canlet.2011.10.024

Cited by 31 publications

(28 citation statements)

References 27 publications

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“…Indeed, prolonged exposure of CCA cells to increasing concentrations of gemcitabine led to a substantial increase in migration and invasion, an effect coupled with the aberrant activation of the FAK/MAPK/NF-κB axis, which is eventually responsible for enhanced MMP-9 production 84 . Similarly, long-term exposure of CCA cell lines or xenografts to cisplatin induced the overactivation of EGFR, and the up-regulation of L1 cell adhesion molecule (L1CAM) 85 , a transmembrane glycoprotein supporting the migratory and invasive potential of neoplastic cholangiocytes 86 . Unfortunately, the modulatory effects of genotoxic therapies further complicate the characterization of the wide and heterogeneous range of molecular mechanisms through which CCA cells gradually adopt an invasive phenotype.…”

Section: Novel Signaling Mechanisms and Trascription Factors Promotinmentioning

confidence: 99%

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

et al. 2018

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The acquisition of invasive functions by tumor cells is a first and crucial step towards the development of metastasis, which nowadays represents the main cause of cancer-related death. Cholangiocarcinoma (CCA), a primary liver cancer originating from the biliary epithelium, typically develops intrahepatic or lymph node metastases at early stages, thus preventing the majority of patients from undergoing curative treatments, consistent with their very poor prognosis. As in most carcinomas, CCA cells gradually adopt a motile, mesenchymal-like phenotype, enabling them to cross the basement membrane, detach from the primary tumor, and invade the surrounding stroma. Unfortunately, little is known about the molecular mechanisms that synergistically orchestrate this pro-invasive phenotypic switch. Autocrine and paracrine signals (cyto/chemokines, growth factors, morphogens) permeating the tumor microenvironment undoubtedly play a prominent role in this context. Moreover, a number of recently identified signaling systems are currently drawing attention as putative mechanistic determinants of CCA cell invasion. They encompass transcription factors, protein kinases and phosphatases, ubiquitin ligases, adaptor proteins, and miRNAs, whose aberrant expression may result from either stochastic mutations or the abnormal activation of upstream pro-oncogenic pathways. Herein, we sought to summarize the most relevant molecules in this field, and to discuss their mechanism of action and potential prognostic relevance in CCA. Hopefully, a deeper knowledge of the molecular determinants of CCA invasiveness will help to identify clinically useful biomarkers and novel druggable targets, with the ultimate goal to develop innovative approaches to the management of this devastating malignancy.

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Section: Novel Signaling Mechanisms and Trascription Factors Promotinmentioning

confidence: 99%

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

et al. 2018

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“…They have different metabolic characteristics due to their different tissue sources[1]. Compared with hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) cells have primary resistance to chemotherapeutic drugs such as cisplatin [2, 3]. In addition, it has been found that reduction–oxidation (REDOX) signaling pathways play a major role in cancer formation and especially in responses to radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS

Sheng

Shen

et al. 2017

PLoS ONE

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The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.

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“…Overexpression of CD171 has been shown to promote tumor cell growth, cell motility and migration as well as angiogenesis [7,8]. Several reports suggest that L1CAM is also involved in apoptosis resistance [6].…”

Section: Discussionmentioning

confidence: 99%

“…Several reports suggest that L1CAM is also involved in apoptosis resistance [6]. Tumors of various sites express this molecule, including neoplasms of the female genital tract, colon, stomach, pancreas, skin, and the kidneys [6][7][8][21][22][23]. Expression is often found at the invasive front of primary tumors [24], strongly supporting a role for L1CAM in metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…CD171, also known as L1CAM, is a 200-kDa transmembrane glycoprotein. It is a neuronal cell adhesion molecule involved in axon guidance and cell migration [5] with a strong implication in treatment-resistant cancers [6][7][8]. L1CAM belongs to the immunoglobulin superfamily of recognition molecules, and participates in heterophilic interactions with other adhesion molecules such as laminin, integrins, proteoglycans and CD24.…”

Section: Introductionmentioning

confidence: 99%

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The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors

Moulla¹,

Miliaras²,

Sioga³

et al. 2013

pjp

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CD24 and CD171 are cell adhesion proteins, which have been shown to be overexpressed in several carcinomas and to be associated with a poor clinical outcome. Our aim was to determine the expression of these two adhesion molecules in ovarian borderline neoplasms. We investigated 50 ovarian borderline tumors (serous, mucinous and endometrioid) as well as 29 benign cystadenomas and 25 carcinomas, which were used as controls. Paraffin sections were stained immunohistochemically for CD24 and CD171, and their expression was recorded in a semi-quantitative manner. In normal epithelium and benign ovarian cystadenomas both the CD24 and CD171 expression was negative to low, while their expression was significantly increased in borderline and malignant ovarian tumors. High-grade carcinomas, and carcinomas with metastases to the omentum presented considerably higher CD24 expression than low-grade carcinomas, and carcinomas without metastases. In addition, a few borderline and many malignant tumors presented cytoplasmic CD24 immunoreactivity, whereas all benign and most borderline tumors showed apical localization of this molecule. In conclusion, borderline tumors and carcinomas of the ovary present increased expression of CD24 and CD171 in relation to their benign counterparts, as is the case in malignant tumors of other organs. Change of staining pattern of CD24 (apical to cytoplasmic) apparently relates to a more aggressive phenotype.

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L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells

Cited by 31 publications

References 27 publications

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS

The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors

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