Abstract 2620: Aquaporin 11 as a new predictive biomarker of overall survival and platinum-based chemotherapy response in lung adenocarcinoma patients

Sharpnack, Michael F.; Carbone, David P.; Dikov, Mikhail M.; Tchekneva, Elena E.

doi:10.1158/1538-7445.am2018-2620

Cited by 3 publications

(3 citation statements)

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“…Clinical trials indicated high expression of AQP8 was associated with better prognoses and overall survival in colon cancer [ 92 ]. AQP11 transcripts, at high levels, have been associated with poor survival in lung adenocarcinoma [ 93 ] but, conversely, better survival in breast cancer [ 94 ], suggesting cancer-specific contributions of different classes of aquaporins. Selective inhibitors for AQPs 8 and 11 remain to be identified; in the interim, interfering RNA knockdown techniques might be used to explore the possible roles of these channels in EC cells.…”

Section: Discussionmentioning

confidence: 99%

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels

Khan,

Lokman,

Oehler

et al. 2023

Cancers

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Aquaporin (AQP) channels in endometrial cancer (EC) cells are of interest as pharmacological targets to reduce tumor progression. A panel of compounds, including AQP1 ion channel inhibitors (AqB011 and 5-(phenoxymethyl) furan-2-carbaldehyde, PMFC), were used to test the hypothesis that inhibition of key AQPs can limit the invasiveness of low- and high-grade EC cells. We evaluated the effects on transwell migration in EC cell lines (Ishikawa, MFE-280) and primary EC cells established from surgical tissues (n = 8). Quantitative PCR uncovered classes of AQPs not previously reported in EC that are differentially regulated by hormonal signaling. With estradiol, Ishikawa showed increased AQPs 5, 11, 12, and decreased AQPs 0 and 4; MFE-280 showed increased AQPs 0, 1, 3, 4, 8, and decreased AQP11. Protein expression was confirmed by Western blot and immunocytochemistry. AQPs 1, 4, and 11 were colocalized with plasma membrane marker; AQP8 was intracellular in Ishikawa and not detectable in MFE-280. AQP1 ion channel inhibitors (AqB011; PMFC) reduced invasiveness of EC cell lines in transwell chamber and spheroid dispersal assays. In Ishikawa cells, transwell invasiveness was reduced ~41% by 80 µM AqB011 and ~55% by 0.5 mM 5-PMFC. In MFE-280, 5-PMFC inhibited invasion by ~77%. In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective. Treatments of cultured primary EC cells with AqB011 or PMFC significantly reduced the invasiveness of both low- and high-grade primary EC cells in transwell chambers. We confirmed the tumors expressed moderate to high levels of AQP1 detected by immunohistochemistry, whereas expression levels of AQP4, AQP8, and AQP11 were substantially lower. The anti-invasive potency of AqB011 treatment for EC tumor tissues showed a positive linear correlation with AQP1 expression levels. In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels

Khan,

Lokman,

Oehler

et al. 2023

Cancers

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“…A follow-on study using matched mRNA expression, survival, and drug response data from TCGA lung adenocarcinoma dataset (N = 369), In this report, Sharpnack et al. have demonstrated that high AQP11 mRNA expression is negatively prognostic in patients with adenocarcinoma of lung (LUAD) ( 199 ). Furthermore, patients with high tumor AQP11 mRNA expression (10.3%) had significantly worse overall survival compared with patients with low AQP11 expression.…”

Section: Role Of Aqps In Human Carcinogenesismentioning

confidence: 90%

Aquaporins in Cancer Biology

Moon

Kang

2022

Front. Oncol.

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Aquaporins (AQPs) are a family of transmembrane water channel proteins, which were initially characterized as a novel protein family that plays a vital role in transcellular and transepithelial water movement. AQP1, AQP2, AQP4, AQP5, and AQP8 are primarily water selective, whereas AQP3, AQP7, AQP9, and AQP10 (called “aqua-glyceroporins”) also transport glycerol and other small solutes. Recently, multiple reports have suggested that AQPs have important roles in cancer cell growth, migration, invasion, and angiogenesis, each of which is important in human carcinogenesis. Here, we review recent data concerning the involvement of AQPs in tumor growth, angiogenesis, and metastasis and explore the expression profiles from various resected cancer samples to further dissect the underlying molecular mechanisms. Moreover, we discuss the potential role of AQPs during the development of genomic instability and performed modeling to describe the integration of binding between AQPs with various SH3 domain binning adaptor molecules. Throughout review and discussion of numerous reports, we have tried to provide key evidence that AQPs play key roles in tumor biology, which may provide a unique opportunity in designing a novel class of anti-tumor agents.

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“…AQP4 has been implicated in glioma cell migration and their resistance to chemotherapy (Lan et al, 2017). Similarly (Dong et al, 2016), AQP11 is partly responsible for the variations in lung cancer response to chemotherapy (Sharpnack et al, 2018 | 6121 PI3K/AKT, EGF, and some other proliferative signaling pathways.…”

Section: Cancer and Aqp1 Aqp3 Aqp4 Aqp5 And Aqp11mentioning

confidence: 99%

Aquaporins and diseases pathogenesis: From trivial to undeniable involvements, a disease‐based point of view

Ala

Jafari

Hajiabbasi

et al. 2021

Journal Cellular Physiology

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Aquaporins (AQPs), as transmembrane proteins, were primarily identified as water channels with the ability of regulating the transmission of water, glycerol, urea, and other small-sized molecules. The classic view of AQPs involvement in therapeutic plan restricted them and their regulators into managing only a narrow spectrum of the diseases such as diabetes insipidus and the syndrome of inappropriate ADH secretion. However, further investigations performed, especially in the third millennium, has found that their cooperation in water transmission control can be manipulated to handle other burden-imposing diseases such as cirrhosis, heart failure, Meniere's disease, cancer, bullous pemphigoid, eczema, and Sjögren's syndrome.

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Abstract 2620: Aquaporin 11 as a new predictive biomarker of overall survival and platinum-based chemotherapy response in lung adenocarcinoma patients

Cited by 3 publications

References 0 publications

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels

Aquaporins in Cancer Biology

Aquaporins and diseases pathogenesis: From trivial to undeniable involvements, a disease‐based point of view

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