Na+/H+ exchanger‐dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation‐associated phenotypes

@article{Reshkin2000NaHEI,
  title={Na+/H+ exchanger‐dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation‐associated phenotypes},
  author={Stephan Joel Reshkin and Antonia Bellizzi and Sandra Caldeira and Valentina Albarani and Ilaria Malanchi and Manuela Poignee and Marianna Alunni-Fabbroni and Valeria Casavola and Massimo Tommasino},
  journal={The FASEB Journal},
  year={2000},
  volume={14},
  pages={2185 - 2197}
}
In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is transformation specific. In NIH3T3 cells in which transformation can be turned on and followed by induction of the HPV16 E7 oncogene expression, we demonstrate that cytoplasmic… 
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Na-H Exchange-dependent Increase in Intracellular pH Times G2/M Entry and Transition*

It is shown that NHE1 activity and pHi regulate the timing of G2/M entry and transition, and it is suggested that increases in pHi at the completion of S phase may constitute a previously unrecognized checkpoint for progression to G2 and mitosis.

Intracellular pH regulation by Na⁺/H⁺ exchanger-1 (NHE1) is required for growth factor-induced mammary branching morphogenesis.

Regulation of the Na+/H+ Exchanger (NHE1) in Breast Cancer Metastasis.

The importance of these regulatory sites and what role they may play in the disrupted functionality of NHE1 in breast cancer metastasis are reviewed.

Na+-H+ exchanger, pH regulation and cancer.

Recent progress in understanding the role the NHE1 in determining tumor progression and invadopodia- guided invasion/metastasis is presented and recent patents for N HE1 inhibitors and novel therapeutic protocols for anti-NHE1 pharmacological approaches are presented.

Role of pHi, and proton transporters in oncogene-driven neoplastic transformation

The understanding of the role of pH and the NHE1 in driving transformation, in determining the first appearance of the cancer ‘hallmark’ characteristics and how the use of pharmacological approaches targeting pH/NHE1 may open up new avenues for efficient treatments even during the first steps of cancer development are presented.

Na+/H+ Exchangers and RhoA Regulate Acidic Extracellular pH‐Induced Lysosome Trafficking in Prostate Cancer Cells

Interestingly, using the more specific NHE1 and NHE3 inhibitors, cariporide and s3226 respectively, it is shown that multiple NHE isoforms are involved in acidic pHe‐induced lysosome trafficking and exocytosis, suggesting compensation by other NHE family members.

Na (+)/H (+)exchange in the tumour microenvironment: does NHE1 drive breast cancer carcinogenesis?

Na(+)/H(+)flux, as mediated by the sodium-hydrogen exchanger isoform 1 (NHE1), a major ion transporter involved in tumourigenesis, is discussed and the potential for targeting NHE1 in the development of novel chemotherapeutic applications is explored.

The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth

The above findings suggest that an increase in free-form eEF1A under alkaline conditions plays a critical role in alkalinization-induced cell growth.

Hypoxia-Induced Invadopodia Formation Involves Activation of NHE-1 by the p90 Ribosomal S6 Kinase (p90RSK)

It is shown that hypoxia stimulates the formation of invadopodia as well as the invasive ability of cancer cells, and establishes p90RS kinase as a link between Hypoxia and the acidic microenvironment of tumors.

The Na+/H+ exchanger NHE1 in stress-induced signal transduction: implications for cell proliferation and cell death

New findings implicating NHE1 activation as a central signaling event activated by stress conditions and modulating cell proliferation and death are presented and discussed.
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