Relationship between expression of drug-resistance factors and drug sensitivity in normal human renal proximal tubular epithelial cells in comparison with renal cell carcinoma

Asakura, Tadashi; Imai, Akiko; Ohkubo-Uraoka, Noriko; Kuroda, Mayuko; Iidaka, Yoko; Uchida, Kumiko; Shibasaki, Toshiaki; Ohkawa, Kiyoshi

doi:10.3892/or.14.3.601

Cited by 20 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of the gene encoding the small c subunit, upregulation in response to drug treatment can be caused by an increase in transcription or enhanced mRNA stability (199). However, it is important to note that expression of V-ATPase genes does not always correlate with drug resistance, even when cotreatment with V-ATPase inhibitors and chemotherapies overcomes resistance (8). Expansion of the lysosomal compartment has also been observed to correlate with drug resistance due to the increased capacity to sequester drugs.…”

Section: Function Of V-atpases In Cancermentioning

confidence: 97%

“…Cathepsins are proteases that normally reside in lysosomes and that require a low pH for both their activity and their proteolytic activation (115,180,190), while MMPs, although not directly pH dependent, can nevertheless be activated at low pH, in particular by cathepsin-dependent cleavage (83,166,190). Both cathepsins and MMPs are secreted by tumor cells and have been shown to participate in invasion (8,54,110,115,143,185). Moreover, both intracellular and plasma membrane V-ATPases may contribute to the promotion of protease activity.…”

Section: Mechanism Of V-atpase Promotion Of Tumor Cell Invasion Anmentioning

confidence: 98%

See 1 more Smart Citation

The Function of V-ATPases in Cancer

Stransky

Cotter

Forgac

2016

Physiological Reviews

234

268

View full text Add to dashboard Cite

The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP hydrolysis to proton transport into intracellular compartments and across the plasma membrane. They function in a wide array of normal cellular processes, including membrane traffic, protein processing and degradation, and the coupled transport of small molecules, as well as such physiological processes as urinary acidification and bone resorption. The V-ATPases have also been implicated in a number of disease processes, including viral infection, renal disease, and bone resorption defects. This review is focused on the growing evidence for the important role of V-ATPases in cancer. This includes functions in cellular signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in the highly acidic environment of tumors, aiding the development of drug resistance, as well as crucial roles in tumor cell invasion, migration, and metastasis. Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V-ATPases that function in cancer cells.

show abstract

Section: Function Of V-atpases In Cancermentioning

confidence: 97%

Section: Mechanism Of V-atpase Promotion Of Tumor Cell Invasion Anmentioning

confidence: 98%

The Function of V-ATPases in Cancer

Stransky

Cotter

Forgac

2016

Physiological Reviews

234

268

View full text Add to dashboard Cite

show abstract

“…Mutations in the coding regions of TERT can affect telomerase activity and telomere length, and generate severe clinical phenotypes, including bone marrow failure syndromes and a substantive increase in cancer frequency [8]. Although the function of the CLPTM1L is largely unknown, studies have demonstrated that it may be involved in the apoptotic response to genotoxic stress induced by cisplatin, as it encodes a transcript whose over-expression has been shown to induce apoptosis in cisplatin-resistant-sensitive cells [9], [10], [11], [12]. Moreover, the CLPTM1L variants are hypothesized to enhance the metabolic activation of the reactive metabolites and/or formation and persistence of DNA adducts [13].…”

Section: Introductionmentioning

confidence: 99%

TERT-CLPTM1L Polymorphism rs401681 Contributes to Cancers Risk: Evidence from a Meta-Analysis Based on 29 Publications

Yin

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundSome common genetic variants of TERT-CLPTM1L gene, which encode key protein subunits of telomerase, have been suggested to play a crucial role in tumorigenesis. The TERT-CLPTM1L polymorphism rs401681 was of special interest for cancers risk but with inconclusive results.Methodology/Principal FindingsWe performed a comprehensive meta-analysis of 29 publications with a total of 91263 cases and 735952 controls. We assessed the strength of the association between rs401681 and overall cancers risk and performed subgroup analyses by cancer type, ethnicity, source of control, sample size and expected power. Rs401681 C allele was found to be associated with marginally increased cancers risk, with per allele OR of 1.04 (95%CI = 1.00–1.08, P heterogeneity<0.001) and an expected power of 1.000. Following further stratified analyses, the increased cancers risk were discovered in subgroups of lung, bladder, prostate, basal cell carcinomas and Asians, while a declined risk of pancreatic cancer and melanoma were detected.Conclusions/SignificanceThese findings suggested that rs401681 C allele was a low-penetrance risk allele for the development of cancers of lung, bladder, prostate and basal cell carcinoma, but a potential protective allele for melanoma and pancreatic cancer.

show abstract

“…A high expression of this gene was observed in a renal carcinoma cell line when compared to normal cells, as well as in a cell line of ovary cancer resistant to treatment with cisplatin (74,75). However, no information is available in the literature on CRR9 expression in head and neck cancer.…”

Section: Discussionmentioning

confidence: 94%