The non‐canonical nuclear functions of key players of the PI3K‐AKT‐MTOR pathway

Gupta, Sakshi; Kumar, Mukund; Chaudhuri, Soumi; Kumar, Arun

doi:10.1002/jcp.30782

Cited by 11 publications

(5 citation statements)

References 163 publications

(279 reference statements)

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“…Importantly, we demonstrated for the first time that the nuclear localization of mTOR was positively associated with higher-grade endometrial cancer and FIGO stages IB-IV. In tumor cells, mTOR inside the nucleus may act as an oncogene and play a role in the regulation of transcription, apoptosis, and mitochondrial oxidation [30,31]. In accordance with our findings, nuclear mTOR has been found to be associated with the progression of different tumor types, such as prostate cancer [32] and multiple myeloma [33].…”

Section: Discussionsupporting

confidence: 89%

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade

Pietrus

Pityński

Waligóra

et al. 2023

IJMS

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Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1–3 and FIGO stages I–IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB–IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms.

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Section: Discussionsupporting

confidence: 89%

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade

Pietrus

Pityński

Waligóra

et al. 2023

IJMS

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“…Activation of PI3K receptors causes phosphorylation of phosphatidylinositol to form phosphatidylinositol 3,4,5-triphosphate as the second messenger, with phosphatidylinositol 4,5-bisphosphate as the substrate. This causes activation of downstream signalling molecules such as AKT [159]. Both RANKL and MCSF activated the PI3K/AKT signalling pathway, which has been shown to regulate osteoclast survival and differentiation [160].…”

Section: Regulating the Mapks/jnk/erk And Pi3k/akt Signalingmentioning

confidence: 99%

Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies

2023

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Resveratrol (RSV) (3,5,4′-trihydroxystilbene) is a stilbene found in abundance in berry fruits, peanuts, and some medicinal plants. It has a diverse range of pharmacological activities, underlining the significance of illness prevention and health promotion. The purpose of this review was to delve deeper into RSV’s bone-protective properties as well as its molecular mechanisms. Several in vivo studies have found the bone-protective effects of RSV in postmenopausal, senile, and disuse osteoporosis rat models. RSV has been shown to inhibit NF-κB and RANKL-mediated osteoclastogenesis, oxidative stress, and inflammation while increasing osteogenesis and boosting differentiation of mesenchymal stem cells to osteoblasts. Wnt/β-catenin, MAPKs/JNK/ERK, PI3K/AKT, FoxOs, microRNAs, and BMP2 are among the possible kinases and proteins involved in the underlying mechanisms. RSV has also been shown to be the most potent SIRT1 activator to cause stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. RSV may, thus, represent a novel therapeutic strategy for increasing bone growth and reducing bone loss in the elderly and postmenopausal population.

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“…The cytoplasmic counterpart of the pathway is considered the canonical route for regulating cellular functions. However, PI3K is also present in the nucleus 35 . Various factors target the pathway and are observed to aberrantly activate the pathway leading to progression of cancer in the patient for example the cancer-testis antigen A-kinase anchor protein 3 (AKAP3) 36 .…”

Section: Cell Intrinsic Pathways Involved In Breast Cancer Plasticitymentioning

confidence: 99%

The Unholy Trinity- Cancer cell plasticity, drug resistance and therapeutic opportunities

Chatterjee

Pulipaka

Subbalakshmi

et al. 2023

Preprint

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Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognised as one of the major contributors to intra-tumoral heterogeneity, a critical factor underlying the progression of malignant tumors which is known to modify tumor response and induce resistance against various modes of therapy thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like MAPK, PI3K, STAT3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition (EMT) and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. Some cancers like breast cancer are known to exhibit a hierarchical organization with cancer stem cells (CSCs) at the pinnacle of the pyramid due to their ability to promote tumorigenesis, metastasis and therapy resistance. CSCs which can undergo phenotypic changes resulting in heterogenous cell populations with differing potential to develop programs necessary for the metastatic process lies at the core of the cancer cell plasticity hypothesis. Our expanding knowledge of this field can lead to the development of more therapeutic strategies that can be used in cancer and other solid tumors that exhibit similar mechanisms of plasticity. This review will explore the current understanding we have of breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease. Keywords: Cancer cell plasticity, Epithelial to Mesenchymal Transition (EMT), therapy resistance, targeted therapy.

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The non‐canonical nuclear functions of key players of the PI3K‐AKT‐MTOR pathway

Cited by 11 publications

References 163 publications

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade

Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies

The Unholy Trinity- Cancer cell plasticity, drug resistance and therapeutic opportunities

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