Prognostic relevance of carbonic anhydrase IX expression is distinct in various subtypes of breast cancer and its silencing suppresses self-renewal capacity of breast cancer cells

Ivanova, Lāsma; Zandberga, Elīna; Siliņa, Karīna; Kalniņa, Zane; Ābols, Artūrs; Endzeliņš, Edgars; Vendina, Ineta; Romanchikova, Nadezhda; Hegmane, Alinta; Trapencieris, Pēteris; Eglītis, Jānis; Linē, Aija

doi:10.1007/s00280-014-2635-1

Cited by 47 publications

(38 citation statements)

References 51 publications

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“…However, the rest of the population can also be affected by I − deficiency, which may result in low TH production and goiter (enlargement of the thyroid gland) (19). Because of the importance of dietary I − intake by humans, international organizations, such as the World Health Organization and others, have made an enormous effort to establish guidelines and policies to promote the consumption of salt supplemented with I − as a strategy for preventing and eradicating IDDs worldwide (20, 21). The oxidized form of I − (i.e., iodine) is covalently incorporated, a process known as iodine organification, into the protein thyroglobulin (TG), a highly glycosylated homodimer synthesized in the endoplasmic reticulum and stored in the colloid of the thyroid.…”

Section: The Importance Of Adequate Iodide Intake and Thyroid Hormonementioning

confidence: 99%

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

Ravera

Reyna-Neyra

Ferrandino

et al. 2017

Annu. Rev. Physiol.

201

197

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Active iodide (I−) transport in both the thyroid and some extrathyroidal tissues is mediated by the N a+/I− symporter (NIS). In the thyroid, NIS-mediated I− uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. The molecular characterization of NIS in 1996 and the use of radioactive I− isotopes have led to significan advances in the diagnosis and treatment of thyroid cancer and provide the molecular basis for studies aimed at extending the use of radioiodide treatment in extrathyroidal malignancies. This review focuses on the most recent finding on I− homeostasis and I− transport deficiency-causin NIS mutations, as well as current knowledge of the structure/function properties of NIS and NIS regulatory mechanisms. We also discuss employing NIS as a reporter gene using viral vectors and stem cells in imaging, diagnostic, and therapeutic procedures.

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Section: The Importance Of Adequate Iodide Intake and Thyroid Hormonementioning

confidence: 99%

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

Ravera

Reyna-Neyra

Ferrandino

et al. 2017

Annu. Rev. Physiol.

201

197

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“…Initial studies in a colorectal carcinoma xenograft model revealed that inhibiting CAIX with different CAIX inhibitors (CAI: acetazolamide, DH348 or 11c) or knockdown of CA9 with shRNA delayed tumor growth and radiosensitized tumor cells (16,17). Furthermore, it has been supposed that the prognostic significance of CAIX expression differs depending on the breast cancer subtype of patients (18).…”

Section: Introductionmentioning

confidence: 99%

Cellular and radiobiological effects of carbonic anhydrase IX in human breast cancer cells

et al. 2019

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Hypoxia-induced carbonic anhydrase IX (CAIX) is involved in intracellular and extracellular pH regulation, which is critical for tumor growth and metastasis. CAIX is overexpressed in breast cancer and is associated with the poor survival of patients after radiotherapy. Therefore, we evaluated the cellular and radiobiological effects of CAIX inhibition in human breast cancer cells. We used CA9 siRNA and the CA inhibitor (CAI) U104, respectively, to inhibit CAIX expression and activity in basal triple-negative MDA-MB-231 and luminal MCF-7 cells under hypoxic conditions. We investigated the effects of CAIX inhibition on CA9 mRNA and CAIX protein level, as well as on CAIX activity, intracellular pH, proliferation, apoptosis, clonogenic survival, migration, cell cycle distribution and radiosensitivity. CA9 siRNA and CAI U104 decreased CA9 mRNA and CAIX protein level in MDA-MB-231 and MCF-7 cells. Furthermore, incubation with CAI U104 significantly decreased carbonic anhydrase activity and reduced the intracellular pH. Additionally, CA9 siRNA or U104 reduced clonogenic survival, migration and the number of cells in the G 0 /G 1 phase, induced apoptosis and demonstrated additive or synergistic effects in combination with irradiation. In conclusion, combination of CAIX inhibition and irradiation is a promising treatment strategy against breast cancer with hypoxia-induced CAIX expression.

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“…KM plotter can be utilized for the analysis of individual genes with clinical results to relapse-free survival and total survival of the patients. So far, a number of genes have been identified and/or validated by KM plotter in lung cancer19202122, breast cancer2223242526272829303132, and ovarian cancer223334. In this study, we used KM plotter database and accessed the prognostic roles of individual Notch receptor mRNA expression in human gastric cancer patients.…”

mentioning

confidence: 99%

Prognostic values of four Notch receptor mRNA expression in gastric cancer

Tang

et al. 2016

Sci Rep

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Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1–4, in gastric cancer patients through “The Kaplan-Meier plotter” (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors’ high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis.

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Prognostic relevance of carbonic anhydrase IX expression is distinct in various subtypes of breast cancer and its silencing suppresses self-renewal capacity of breast cancer cells

Abstract: Inhibition of CAIX reduces the self-renewal capacity of breast cancer cells, and the combination of doxorubicin and CAIX inhibition is an attractive therapeutic strategy in basal-like and triple-negative breast cancer, which warrants further investigations.

Cited by 47 publications

References 51 publications

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

Cellular and radiobiological effects of carbonic anhydrase IX in human breast cancer cells

Prognostic values of four Notch receptor mRNA expression in gastric cancer

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