Epidermal growth factor signalling and bone metastasis

Lü, Xin; Kang, Yibin

doi:10.1038/sj.bjc.6605490

Cited by 70 publications

(53 citation statements)

References 36 publications

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“…The poor prognosis and recurrence of HCC are majorly caused by intrahepatic metastasis [2,3]. A lot of evidence demonstrated that growth factors and cytokines such as transforming growth factor (TGFb) [4], platelet derived growth factor [5] epidermal growth factor (EGF) [6], hepatocyte growth factor (HGF) [7] and extracellular matrix (ECM) [8] secreted in the tumor environment may trigger epithelial mesenchymal transition (EMT), migration and invasion of tumor cells [9]. Delineating the molecular pathways mediating these processes may benefit developing effective targeting strategies for prevention of intrahepatic metastasis of HCC.…”

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2

Cheng

et al. 2011

Clin Exp Metastasis

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The poor prognosis and recurrence of HCC are majorly caused by intrahepatic metastasis. Delineating the molecular pathways mediating these processes may benefit developing effective targeting therapies. Using human hepatoma HepG2 as a model, we have found reactive oxygen species (ROS) may cooperate with protein kinase C (PKC) for sustained ERK phosphorylation and migration of HepG2 induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We further investigated whether integrin signaling is involved. Various antagonists of integrin signaling prevented TPA-induced activation of ERK and PKC, ROS generation and migration of HepG2. On the other hand, TPA-induced phosphorylation of integrin signaling components including focal adhesion kinase (FAK), Src (Tyr416) and paxillin (Tyr31 and Ser178) can be prevented by PKC inhibitor Bisindolylmaleimides (BIS) and antioxidant dithiotheritol (DTT). HepG2 overexpressing PKCα contained elevated phosphorylated paxillin. Also, ROS generator phenazine methosulfate and tert-Butyl hydroperoxide may induce phosphorylation of paxillin and activation of PKC. Taken together, ROS mediated cross talk of PKC and integrin for migration of HepG2 induced by TPA. Furthermore, TPA induced intrahepatic metastasis of HepG2 in SCID mice, which was prevented by BIS or (BIS plus DTT). Elevated phosphorylation of paxillin was observed in tumor of mice treated with TPA as compared with those co-treated with TPA/BIS. In summary, the signal pathways for tumor progression of hepatoma induced by TPA can be established both in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2

Cheng

et al. 2011

Clin Exp Metastasis

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“…epidermal growth factor receptor (EGFR; also called ERBB1 or HER1), ERBB2 (also called HER2, ERBB3 or HER3) and ERBB4 (also called HER4) [79][80][81]. Receptors and ligands of ERBB are frequently overexpressed by carcinoma cells [82], with EGFR and ERBB3 overexpressed in 50-70% of lung, colon and breast carcinoma, ERBB2 in 30% of breast cancer patients, and ERBB4 in 50% of breast cancer patients and 22% of colon cancer patients [79].…”

Section: Npc Regulates Egfr Signal Activator Traffic Into the Nucleusmentioning

confidence: 99%

“…Receptors and ligands of ERBB are frequently overexpressed by carcinoma cells [82], with EGFR and ERBB3 overexpressed in 50-70% of lung, colon and breast carcinoma, ERBB2 in 30% of breast cancer patients, and ERBB4 in 50% of breast cancer patients and 22% of colon cancer patients [79].…”

Section: Npc Regulates Egfr Signal Activator Traffic Into the Nucleusmentioning

confidence: 99%

The role of nuclear pore complex in tumor microenvironment and metastasis

Funasaka

Wong

2011

Cancer Metastasis Rev

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One of the main reasons for cancer mortality is caused by the highly invasive behavior of cancer cells, which often due to aggressive metastasis. Metastasis is mediated by various growth factors and cytokines, operating through numerous signaling pathways. Remarkably, all these metastatic signaling pathways must enter the nucleus through a single gatekeeper, the nuclear pore complex (NPC). NPCs are the only gateway between the cytoplasm and the nucleus. NPCs are among the largest proteinaceous assemblies in the cell and are composed of multiple copies of around 30 different proteins called nucleoporins (Nups). Here we review what is currently known about the NPC and its role in the mechanisms of tumor progression. We will also explore potential strategies to target metastatic pathways by manipulating the karyopherins (importins/exportins) of nucleocytoplasmic traffic through NPCs. / 39

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“…The balance between osteoblasts and osteoclasts can be perturbed by altering the activity of EGF signaling as it stimulates growth of bone metastasis directly by increasing tumor cell proliferation and indirectly with bone stromal cell essential for the metastasis development [Lu and Kang, 2010].…”

Section: Egfr Tkismentioning

confidence: 99%

Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies

D’Antonio

Passaro

Gori³

et al. 2014

Ther Adv Med Oncol

196

162

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Bone metastasis in lung cancerLung cancer is the third most common form of cancer to spread to bone. About 30-40% of patients with lung cancer developed bone metastases during the course of their disease; the median survival time of patients with this secondary lesion is 7 months [Coleman, 2001]. These metastases are associated with significant morbidity, loss of functional independence and reduction in quality of life (QOL) [Berenson et al. 2006]. Bone metastasis accounts for 350,000 cancer patients deaths each year [Mundy, 2002] and in lung cancer is associated with increased social costs due to medical care, hospitalization days and cost of treatment [Botteman et al. 2007].In a retrospective study of 259 nonsmall cell lung cancer (NSCLC) patients, the most common site of skeletal metastases was the spine in 50% of patients, followed by the ribs (27.1%), ilium (10%), sacrum (7.1%), femur (5.7%) and humerus, scapula and sternum (2.9%) [Tsuya et al. 2007]. The prognosis was worse in patients with metastasis to the appendicular bone than in patients with metastases only on an axial bone [Sugiura et al. 2008].Pain is usually the first symptom of lung cancer with bone metastases in 80% of patients [Kosteva and Langer, 2008]. Patients with osseous metastases complain of pain at some point with wide variation in pattern and severity [Delaney et al. 2008]. Many factors are implicated in the pain of osseous metastases but a significant portion of the pain seems to be related to osteoclastic bone resorption. Bone and brain metastasis in lung cancer: recent advances in therapeutic strategiesChiara D'Antonio, Antonio Passaro, Bruno Gori, Ester Del Signore, Maria Rita Migliorino, Serena Ricciardi, Alberto Fulvi and Filippo de Marinis Abstract: Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is ...

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Epidermal growth factor signalling and bone metastasis

Cited by 70 publications

References 36 publications

Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2

Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2

The role of nuclear pore complex in tumor microenvironment and metastasis

Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies

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