Receptor Tyrosine Kinases in Osteosarcoma: Not Just the Usual Suspects

Rettew, Ashley N.; Getty, Patrick J.; Greenfield, Edward M.

doi:10.1007/978-3-319-04843-7_3

Cited by 26 publications

(28 citation statements)

References 133 publications

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“…Over-expression, found in the majority of malignant pleural mesothelioma specimens, was shown to influence patient survival, independently of other established prognostic factors [74]. Axl has been proposed as a therapeutic target also in osteosarcoma, being among the most frequently activated RTK [75]. In keeping with this evidence, Gas6/Axl have been reported to inhibit apoptosis and to promote migration and invasion of osteosarcoma cells [76].…”

Section: Regulation Of Cell Survivalmentioning

confidence: 81%

“…Lung [41,45,49,82,83,84,88,90,91] Breast [55,80,103] Colon [47,57] Liver [44] Pancreas [60] Kidney [39] Melanoma [77][78][79] Cutaneous squamous cell cancer [56] Glioblastoma [48,63,66] Ovarian [68,69] Prostate [70] Esophageal squamous cell [87] Head and neck [81,87] Mesothelioma [72][73][74] Osteosarcoma [75,76] Gastrintestinal stromal (GIST) [8] Myeloid leukemia [9] Acute myeloid leukemia [89] Chronic myeloid leukemia [97] Chronic lymphocytic leukemia B cells [101] 1 The tumor subtypes mentioned in the review are reported. Gas6 is mentioned in Ref.…”

Section: Tumor Type Referencesmentioning

confidence: 99%

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Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells

Corno

Gatti

Lanzi

et al. 2016

CMC

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Aberrant expression and activation of receptor tyrosine kinases (RTK) is a frequent feature of tumor cells that may underlie tumor aggressiveness. Among RTK, Axl, a member of the Tyro3-Axl-Mer family, represents a potential therapeutic target in different tumor types given its over-expression which leads to activation of oncogenic signaling promoting cell proliferation and survival, as well as migration and invasion. Axl can promote aggressiveness of various cell types through PI3K/Akt and/or MAPK/ERK, and its expression can be transcriptionally regulated by multiple factors. Deregulated Axl expression and activation have been shown to be implicated in reduced sensitivity of tumor cells to target-specific and conventional antitumor agents, but the precise mechanism underlying these phenomena are still poorly understood. Several small molecules acting as Axl inhibitors have been reported, and some of them are undergoing clinical investigation. In this review, we describe Axl biological functions, its expression in cancer and in drug-resistant tumor cells and the development of inhibitors tailored to this receptor tyrosine kinase.

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Section: Regulation Of Cell Survivalmentioning

confidence: 81%

Section: Tumor Type Referencesmentioning

confidence: 99%

Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells

Corno

Gatti

Lanzi

et al. 2016

CMC

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“…In the same manner, another study showed that knockdown of Axl increased apoptosis and decreased proliferation, also mediated by downregulation of the Akt pathway [ 97 ]. A recent study unraveled additional RTKs involved in the metastatic potential of osteosarcoma, and after lengthy metastatic-dependent validations Axl came out as a top hit in a metastatic osteosarcoma cell line [ 98 ]. Axl also emerged from another screen for differentially expressed genes in high versus low metastatic osteosarcoma sublines [ 99 ].…”

Section: Tissue and Cell Type-specific Roles For Axlmentioning

confidence: 99%

Axl as a mediator of cellular growth and survival

2014

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The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context.

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“…Although investigated by numerous previous studies, the molecular mechanisms of the etiology and pathogenesis underlying OS remain to be elucidated (19,20). Therefore developing effective therapeutic strategies for the treatment of OS is challenging.…”

Section: Discussionmentioning

confidence: 99%

Expression profile of Twist, vascular endothelial growth factor and CD34 in patients with different phases of osteosarcoma

et al. 2015

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Abstract. The aim of the present study was to investigate the clinical significance of Twist, vascular endothelial growth factor (VEGF) and CD34 expression in osteosarcoma (OS) in order to elucidate potential therapeutic targets for the treatment of OS. Immunohistochemistry was performed to detect the protein expression of Twist, VEGF and CD34 in OS and osteochondroma (OC) tissues. The ratio of the protein expression of Twist and VEGF in OS and OC tissues as well as at different phases of OS was compared using chi-squared tests. Microvessel density (MVD), as determined by CD34 labeling, in OS and OC tissue as well as at different phases of OS was compared using the Student's t-test. In addition, associations between Twist, VEGF and MVD were assessed using the Spearman's rank correlation test. The results revealed that out of the 32 OS tissues examined, 56.25% exhibited Twist positive expression, 71.88% exhibited VEGF positive expression and the MVD was increased compared with that of the OC tissue. The positive rate of Twist and VEGF expression in phase III OS tissues was significantly increased compared with that in phase I/II OS tissues (Twist: χ 2

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Receptor Tyrosine Kinases in Osteosarcoma: Not Just the Usual Suspects

Cited by 26 publications

References 133 publications

Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells

Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells

Axl as a mediator of cellular growth and survival

Expression profile of Twist, vascular endothelial growth factor and CD34 in patients with different phases of osteosarcoma

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