Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers

Khan, Sidra; Ricciardelli, Carmela; Yool, Andrea J.

doi:10.3390/cells10020215

Cited by 16 publications

(18 citation statements)

References 185 publications

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“…Delicate regulation of intracellular levels of H 2 O 2 opens possibilities in the stimulation of proliferation and survival mechanism for tumour cells, leading to resistance and increased mobility. Aquaporins were found to be upregulated in numerous tumours [ 28 , 75 , 76 ] opening possibilities to target them as a part of tumour therapy. The exact mechanisms and signalling pathways affected by aquaporins are still to be determined, but it is not a simple and straightforward interaction.…”

Section: Aquaporins Oxidative Stress and Cancermentioning

confidence: 99%

AQP3 and AQP5—Potential Regulators of Redox Status in Breast Cancer

Milković

Gašparović

2021

Molecules

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Breast cancer is still one of the leading causes of mortality in the female population. Despite the campaigns for early detection, the improvement in procedures and treatment, drastic improvement in survival rate is omitted. Discovery of aquaporins, at first described as cellular plumbing system, opened new insights in processes which contribute to cancer cell motility and proliferation. As we discover new pathways activated by aquaporins, the more we realize the complexity of biological processes and the necessity to fully understand the pathways affected by specific aquaporin in order to gain the desired outcome–remission of the disease. Among the 13 human aquaporins, AQP3 and AQP5 were shown to be significantly upregulated in breast cancer indicating their role in the development of this malignancy. Therefore, these two aquaporins will be discussed for their involvement in breast cancer development, regulation of oxidative stress and redox signalling pathways leading to possibly targeting them for new therapies.

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Section: Aquaporins Oxidative Stress and Cancermentioning

confidence: 99%

AQP3 and AQP5—Potential Regulators of Redox Status in Breast Cancer

Milković

Gašparović

2021

Molecules

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“…In breast cancer, AQP expression is significantly associated with overall survival and relapse free survival (18,19). AQPs impact tumor growth and metastasis by regulating proliferation, migration, and angiogenesis in mammary tumors and breast cancer cell lines (12,(19)(20)(21). Although we are beginning to understand the importance of AQPs in cancer, further elucidation of AQP structure and function will shed light into the additional and unexpected roles of these transport proteins and how their dysregulation can lead to disease.…”

Section: Introductionmentioning

confidence: 99%

Aquaporins: New players in breast cancer progression and treatment response

et al. 2022

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Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patient’s response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment.

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“…However, additional research, particularly in the third millennium, for instance a study by Ala [ 106 ], has revealed that their cooperation in water transmission control can be manipulated to address other burden-imposing diseases, including cirrhosis, heart failure, Meniere’s disease, cancer, bullous pemphigoid, eczema, and Sjogren’s syndrome. Khan [ 103 ] shows the important association between breast cancer and aquaporins, underlining that AQPs 1, 3, and 5 are highly expressed in breast, endometrial, and ovarian cancers, consistent with their gene regulation by estrogen response elements. Bystrup [ 107 ] considers that understanding the underlying molecular mechanisms of how AQP5 contributes to cancer development and progression is crucial for the potential use of AQP5 as a prognostic biomarker and for the development of targeted intervention strategies for the treatment of breast cancer patients.…”

Section: Resultsmentioning

confidence: 99%

“…Future Trends and Potential Therapeutic Targets in Breast Cancer 3.6.1. Aquaporins Aquaporins (AQPs) are membrane channels that belong to the large family of major intrinsic proteins (MIPs), of which there are thirteen classes with tissue-specific distributions in humans, as summed up by Khan [103] and Magouliotis [104]. As important physiological modulators of water and solute homeostasis, mutations and dysfunctions in aquaporins have been linked to pathologies in all major organs.…”

Section: Prognosismentioning

confidence: 99%

An Update on the General Features of Breast Cancer in Male Patients—A Literature Review

et al. 2022

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Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and (c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and (d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. Randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

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Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers

Cited by 16 publications

References 185 publications

AQP3 and AQP5—Potential Regulators of Redox Status in Breast Cancer

AQP3 and AQP5—Potential Regulators of Redox Status in Breast Cancer

Aquaporins: New players in breast cancer progression and treatment response

An Update on the General Features of Breast Cancer in Male Patients—A Literature Review

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