BRCA1 overexpression attenuates breast cancer cell growth and migration by regulating the pyruvate kinase M2-mediated Warburg effect <i>via</i> the PI3K/AKT signaling pathway

Liu, Xiuli; Liu, Hanxu; Zeng, Lingyu; Lv, Yuetao

doi:10.7717/peerj.14052

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…Dysregulation of let-7b has also been observed in BRCA2 germ-line mutation carriers between invasive breast cancer and asymptomatic normal breast tissue [ 44 ]. Furthermore, BRCA1 has been found to repress HK2 expression, reducing glycolysis and attenuating BC cell migration [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis

Li¹,

Zhang²,

Lin

et al. 2023

Cell Death Discov.

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Hexokinase 2 (HK2), a critical rate-limiting enzyme in the glycolytic pathway catalyzing hexose phosphorylation, is overexpressed in multiple human cancers and associated with poor clinicopathological features. Drugs targeting aerobic glycolysis regulators, including HK2, are in development. However, the physiological significance of HK2 inhibitors and mechanisms of HK2 inhibition in cancer cells remain largely unclear. Herein, we show that microRNA-let-7b-5p (let-7b-5p) represses HK2 expression by targeting its 3′-untranslated region. By suppressing HK2-mediated aerobic glycolysis, let-7b-5p restrains breast tumor growth and metastasis both in vitro and in vivo. In patients with breast cancer, let-7b-5p expression is significantly downregulated and is negatively correlated with HK2 expression. Our findings indicate that the let-7b-5p/HK2 axis plays a key role in aerobic glycolysis as well as breast tumor proliferation and metastasis, and targeting this axis is a potential therapeutic strategy for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis

Li¹,

Zhang²,

Lin

et al. 2023

Cell Death Discov.

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“…Intriguingly, a switch from PKM1 to PKM2 has been detected in various cancers, and a reverse isoform shift from PKM2 to PKM1 has been found to inhibit aerobic glycolysis and reduce tumorigenesis in multiple xenograft models [71]. In particular, recent findings point to an Akt-dependent pro-tumor modulation of PKM2 [72][73][74][75][76][77], which has also emerged as an upstream regulator of the PI3K/Akt pathway itself [78][79][80][81]; in particular, it seems to be able to activate mTORC1 by interacting with Akt1 substrate 1 (Akt1S1) [82]. In this context, aberrant PKM2 expression has been widely associated with poor prognosis in patients with solid tumors of the digestive system, such as esophageal, gastric, colorectal and liver carcinoma [83][84][85].…”

Section: The Pi3k/akt Cascade and Glucose Metabolism In Cancermentioning

confidence: 99%

The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer

Fontana,

Giannitti,

Marchesi

et al. 2024

Int. J. Biol. Sci.

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Aberrant activation of the PI3K/Akt pathway commonly occurs in cancers and correlates with multiple aspects of malignant progression. In particular, recent evidence suggests that the PI3K/Akt signaling plays a fundamental role in promoting the so-called aerobic glycolysis or Warburg effect, by phosphorylating different nutrient transporters and metabolic enzymes, such as GLUT1, HK2, PFKB3/4 and PKM2, and by regulating various molecular networks and proteins, including mTORC1, GSK3, FOXO transcription factors, MYC and HIF-1α. This leads to a profound reprogramming of cancer metabolism, also impacting on pentose phosphate pathway, mitochondrial oxidative phosphorylation, de novo lipid synthesis and redox homeostasis and thereby allowing the fulfillment of both the catabolic and anabolic demands of tumor cells. The present review discusses the interactions between the PI3K/Akt cascade and its metabolic targets, focusing on their possible therapeutic implications.

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“…Continuous aerobic glycolysis has been demonstrated to trigger oncogene development in the cancer cells. Aerobic glycolysis is known as the Warburg effect and is one of the tumor hallmarks (Liu et al, 2022a). The enhanced Warburg effect is closely linked to EMT and (2021b) reported that zinc finger E-box-binding homeobox 1 (ZEB1), predicting worse overall survival in cancer patients, facilitated tumorigenesis and metastasis of HCC by enhancing the Warburg effect.…”

Section: Hif-1α Facilitates the Progression Of Hcc By Promoting The W...mentioning

confidence: 99%

“…Continuous aerobic glycolysis has been demonstrated to trigger oncogene development in the cancer cells. Aerobic glycolysis is known as the Warburg effect and is one of the tumor hallmarks ( Liu et al, 2022a ). The enhanced Warburg effect is closely linked to EMT and poor patient prognosis in multiple cancer, including HCC.…”

Section: Hif-1α Facilitates the Progression Of Hcc By Promoting The W...mentioning

confidence: 99%

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Xiao

Liu

et al. 2023

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

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BRCA1 overexpression attenuates breast cancer cell growth and migration by regulating the pyruvate kinase M2-mediated Warburg effect via the PI3K/AKT signaling pathway

Cited by 5 publications

References 34 publications

Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis

Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis

The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

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