Imatinib-Mediated Inactivation of Akt Regulates ABCG2 Function in Head and Neck Squamous Cell Carcinoma

Chu, Theresa S.; Chen, Jocelyn S.; López, José García; Pardo, Francisco S.; Aguilera, Joseph; Ongkeko, Weg M.

doi:10.1001/archotol.134.9.979

Cited by 19 publications

(15 citation statements)

References 12 publications

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“…41,42 The function of ABC transport proteins has been found to be affected by the activity of cell signaling pathways, for example the inhibition of the elevated Akt activity of tumor cells has been shown to downregulate ABCG2 expression and efflux activity. 41,42 Interestingly we have also established that heparin treatment of MCF-7, MDA-MB-231, and CSCs cell lines for 30 min reduces the level of intracellular phosphorylation including the level of p-Akt 12 opening up the possibility that heparin treatment may also regulate ABC transporter system through inhibition of Akt activity. There are also reports of LRP binding several phosphatases and kinases including PTEN, SHP-2, as well as ERK, and evidence suggesting that LRP might be involved in the regulation of cell signaling pathways including the PI3K/Akt and the MAPK pathways.…”

Section: Discussionmentioning

confidence: 99%

Binding and inhibition of drug transport proteins by heparin

Chen

Scully

Petralia

et al. 2013

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Binding and inhibition of drug transport proteins by heparin

Chen

Scully

Petralia

et al. 2013

Cancer Biology & Therapy

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“…Subpopulations of stem-like cells expressing BCRP were found in cell lines or primary tumor samples from a wide assortment of solid tumors, including head and neck cancer [205–207], breast carcinoma [202], small cell and non-small cell lung cancer [208–212], gastrointestinal cancers including pancreatic [213, 214], colon [215, 216] and hepatocellular [217–219], ovarian cancer [220], gliomas [221, 222], malignant peripheral nerve sheath tumors [223], osteosarcoma [224, 225], prostate cancer [226], Ewing’s sarcoma [227], odontogenic tumors [228], transitional cell carcinoma of the bladder [229], and neuroblastoma [230]. Details of these findings will be discussed within individual tumor types in the ensuing paragraphs.…”

Section: Section 5 Recent Findings In Solid Tumorsmentioning

confidence: 99%

Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance

Natarajan¹,

Xie²,

Baer³

et al. 2012

Biochemical Pharmacology

358

273

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Since cloning of the ATP-binding cassette (ABC) family member breast cancer resistance protein (BCRP/ABCG2) and its characterization as a multidrug resistance efflux transporter in 1998, BCRP has been the subject of more than two thousand scholarly articles. In normal tissues, BCRP functions as a defense mechanism against toxins and xenobiotics, with expression in the gut, bile canaliculi, placenta, blood-testis and blood-brain barriers facilitating excretion and limiting absorption of potentially toxic substrate molecules, including many cancer chemotherapeutic drugs. BCRP also plays a key role in heme and folate homeostasis, which may help normal cells survive under conditions of hypoxia. BCRP expression appears to be a characteristic of certain normal tissue stem cells termed “side population cells,” which are identified on flow cytometric analysis by their ability to exclude Hoechst 33342, a BCRP substrate fluorescent dye. Hence, BCRP expression may contribute to the natural resistance and longevity of these normal stem cells. Malignant tissues can exploit the properties of BCRP to survive hypoxia and to evade exposure to chemotherapeutic drugs. Evidence is mounting that many cancers display subpopulations of stem cells that are responsible for tumor self-renewal. Such stem cells frequently manifest the “side population” phenotype characterized by expression of BCRP and other ABC transporters. Along with other factors, these transporters may contribute to the inherent resistance of these neoplasms and their failure to be cured.

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“…The localization of ABCG2 may be regulated in part by cell signaling pathways such as the phosphatidyl inositol 3-kinase (PI3K)/ g-Akt murine thymoma viral oncogene homolog (Akt) pathway. In fact, inhibition of both PI3K (Misra et al, 1998) and Akt (Chu et al, 2008) has been shown to cause ABCG2 translocation from the plasma membrane to an intracellular compartment. Moreover, ABCG2 may also be present in the membranes of acidic vesicles (e.g., lysosomes), as colocalization studies with Lysotracker demonstrated sequestration of mitoxantrone in acidic vesicles of both S1 cells and the S1-M1-80 subline that expresses high ABCG2 levels (Litman et al, 2000).…”

Section: Abcg2 In Chemoresistancementioning

confidence: 99%