Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

White, Katharine A.; Grillo-Hill, Bree K.; Barber, Diane L.

doi:10.1242/jcs.195297

Cited by 263 publications

(296 citation statements)

References 108 publications

Supporting

Mentioning

282

Contrasting

Unclassified

Order By: Relevance

“…These findings add to an emerging list of tumorigenic behaviors enabled by the established higher pHi of cancer cells (5). We previously described how the higher pHi of cancers increases cell proliferation and promotes hyperplasia and metastatic progression (2, 4).…”

Section: Discussionmentioning

confidence: 56%

See 1 more Smart Citation

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins

et al. 2017

Self Cite

View full text Add to dashboard Cite

The intracellular pH (pHi) of most cancers is constitutively higher than that of normal cells and enhances proliferation and cell survival. We found that increased pHi enabled the tumorigenic behaviors caused by somatic arginine-to-histidine mutations, which are frequent in cancer and confer pH sensing not seen with wild-type proteins. Experimentally raising the pHi increased the activity of R776H mutant epidermal growth factor receptor (EGFR-R776H), thereby increasing proliferation and causing transformation in fibroblasts. An Arg-to-Gly mutation did not confer these effects. Molecular dynamics simulations of EGFR suggested that decreased protonation of His776 at high pH causes conformational changes in the αC helix that may stabilize the active form of the kinase. An Arg-to-His, but not Arg-to-Lys, mutation in the transcription factor p53 (p53-R273H) decreased its transcriptional activity and attenuated the DNA damage response in fibroblasts and breast cancer cells with high pHi. Lowering pHi attenuated the tumorigenic effects of both EGFR-R776H and p53-R273H. Our data suggest that some somatic mutations may confer a fitness advantage to the higher pHi of cancer cells.

show abstract

Section: Discussionmentioning

confidence: 56%

“…This increased pHi can enable tumorigenic properties, such as increased proliferation, cell survival, and metastasis (1–5). Studies suggest increased pHi may be both a cause and a consequence of tumor cell evolution (6).…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, seminal studies have displayed the measurement of tumorigenicity of breast cancer cells through silicon resonant microelectromechanical systems sensors and Atomic force microscopy . Other physiological characteristic features that can affect the texture of the cell structure are dysregulated intracellular pH dynamics . The over expression of P‐glycoprotein and other ion channels in the chemoresistant cells alter the ionic efflux and influx from inside and outside of the cell .…”

Section: Resultsmentioning

confidence: 99%

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Almabadi

Nagesh

Sahay

et al. 2018

Journal of Biophotonics

View full text Add to dashboard Cite

As cancer progresses, macromolecules, such as DNA, RNA or lipids, inside cells undergo spatial structural rearrangements and alterations. Mesoscopic light transport-based optical partial wave spectroscopy (PWS) was recently introduced to quantify changes in the nanoscale structural disorder in biological cells. The PWS measurement is performed using a parameter termed as "disorder strength" (L ), which represents the degree of nanoscale structural disorder inside the cells. It was shown that cancerous cells have higher disorder strength than normal cells. In this work, we first used the PWS to analyze the hierarchy of different types of prostate cancer cells, namely, C4-2, DU-145 and PC-3, by quantifying their average disorder strengths. Results expectedly showed that L values increases in accordance with the increasing aggressiveness/tumorigenicity levels of these cells. Using the L parameter, we then analyzed the chemoresistance properties of these prostate cancer cells to docetaxel drug compared to their chemosensitivity. Results show that chemoresistant cancer cells have increased L values, that is, higher disorder strength, relative to chemosensitive cancer cells. Thus, use of the L metric can be effective in determining the efficacy of particular chemotherapy.

show abstract

“…A long‐held view is that pHi is constitutively maintained between 7.2 and 7.4 in normal mammalian cells and only dysregulated from this narrow range in diseases, including being constitutively increased in cancer and decreased in neurodegenerative disorders . However, emerging evidence indicates there are transient increases in pHi in normal mammalian cells during cell cycle progression , directional migration , and differentiation .…”

Section: Intracellular Phmentioning

confidence: 99%

Cell fate decisions: emerging roles for metabolic signals and cell morphology

et al. 2017

View full text Add to dashboard Cite

Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studies have found that other aspects of cell biology also make important contributions to regulating cell fate decisions. These cues can have a permissive or instructive role and are integrated into the larger network of signaling, functioning both upstream and downstream of developmental signaling pathways. Here, we summarize recent insights into how cell fate decisions are influenced by four aspects of cell biology: metabolism, reactive oxygen species (ROS), intracellular pH (pHi), and cell morphology. For each topic, we discuss how these cell biological cues interact with each other and with protein-based mechanisms for changing gene transcription. In addition, we highlight several questions that remain unanswered in these exciting and relatively new areas of the field.

show abstract

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

Cited by 263 publications

References 108 publications

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins

Optical study of chemotherapy efficiency in cancer treatment via intracellular structural disorder analysis using partial wave spectroscopy

Cell fate decisions: emerging roles for metabolic signals and cell morphology

Contact Info

Product

Resources

About