Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis

Wu, Di; Yu, Hongqiang; Xiong, Haojun; Zhang, Yujun; Lin, Xiaotong; Zhang, Jie; Wu, Wu; Wang, Teng; Liu, Xiaoyu; Xie, Chuan‐Ming

doi:10.3389/fonc.2021.743824

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…The simultaneous presence of bafilomycin A1 and NAADP resulted in a stronger inhibition of Na + /K + ATPase activity in mouse NK/Ly cells [13]. There is a favorable correlation between the expression levels of the sodium pump-α3 subunit and metastasis in colorectal cancer [45]. Thus, inhibition of Na + /K + ATPase could significantly inhibit the migration of colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

Bychkova,

Bychkov,

Dordevic

et al. 2024

IJMS

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Bafilomycin A1 inhibits V-type H+ ATPases on the molecular level, which acidifies endo-lysosomes. The main objective of the study was to assess the effect of bafilomycin A1 on Ca2+ content, NAADP-induced Ca2+ release, and ATPase activity in rat hepatocytes and human colon cancer samples. Chlortetracycline (CTC) was used for a quantitative measure of stored calcium in permeabilized rat hepatocytes. ATPase activity was determined by orthophosphate content released after ATP hydrolysis in subcellular post-mitochondrial fraction obtained from rat liver as well as from patients’ samples of colon mucosa and colorectal cancer samples. In rat hepatocytes, bafilomycin A1 decreased stored Ca2+ and prevented the effect of NAADP on stored Ca2+. This effect was dependent on EGTA–Ca2+ buffers in the medium. Bafilomycin A1 significantly increased the activity of Ca2+ ATPases of endoplasmic reticulum (EPR), but not plasma membrane (PM) Ca2+ ATPases in rat liver. Bafilomycin A1 also prevented the effect of NAADP on these pumps. In addition, bafilomycin A1 reduced Na+/K+ ATPase activity and increased basal Mg2+ ATPase activity in the subcellular fraction of rat liver. Concomitant administration of bafilomycin A1 and NAADP enhanced these effects. Bafilomycin A1 increased the activity of the Ca2+ ATPase of EPR in the subcellular fraction of normal human colon mucosa and also in colon cancer tissue samples. In contrast, it decreased Ca2+ ATPase PM activity in samples of normal human colon mucosa and caused no changes in colon cancer. Bafilomycin A1 decreased Na+/K+ ATPase activity and increased basal Mg2+ ATPase activity in normal colon mucosa samples and in human colon cancer samples. It can be concluded that bafilomycin A1 targets NAADP-sensitive acidic Ca2+ stores, effectively modulates ATPase activity, and assumes the link between acidic stores and EPR. Bafilomycin A1 may be useful for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

Bychkova,

Bychkov,

Dordevic

et al. 2024

IJMS

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show abstract

“…For example, Kuhn et al (2023) discovered that IGFBP3 inhibited lung cancer cell invasion and proliferation and was linked to the patients’ enhanced survival. Additionally, studies have demonstrated that IGFBP3 regulates additional components of the insulin signaling pathway besides IGF-I/II, such as protein kinase B (PKB/Akt) and insulin receptor substrate (IRS) proteins ( Liu et al, 2021 ; Wu et al, 2021 ; Li et al, 2021 ). Additionally, previous reports have indicated that elevated IGFBP3 levels are correlated with reduced insulin sensitivity and lower insulin secretion rates ( D’Addio et al, 2022 ), and inhibition of insulin signaling axis and insulin-like growth factor ( Wang et al, 2023 ), in alignment with our findings.…”

Section: Discussionmentioning

confidence: 99%

ULK2 suppresses ovarian cancer cell migration and invasion by elevating IGFBP3

Chen,

Shao,

Liu

et al. 2024

PeerJ

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Background Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer. Methods ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation. Results Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells. Conclusions In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer.

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Targeted Delivery of PD‐L1‐Derived Phosphorylation‐Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment

Guo

Jing

et al. 2022

Adv Healthcare Materials

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Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle

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Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis

Cited by 4 publications

References 45 publications

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

ULK2 suppresses ovarian cancer cell migration and invasion by elevating IGFBP3

Targeted Delivery of PD‐L1‐Derived Phosphorylation‐Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment

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