BCKDK Promotes Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway

Li, Huashun; Yu, Dongyang; Li, Lianbing; Xiao, Junhui; Zhu, Yiwen; Liu, Yi; Mou, Li; Tian, Yafei; Chen, Linbo; Zhu, Feng; Duan, Qiuhong; Xue, Peipei

doi:10.1155/2022/3691635

Cited by 7 publications

(6 citation statements)

References 58 publications

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“…A study conducted by Li et al showed that BCKDK was highly expressed in patients with advanced pathological grade ovarian cancer. This ectopic expression of BCKDK promoted the proliferation and migration of OC cells [199].…”

Section: Amino Acid Metabolismmentioning

confidence: 91%

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

et al. 2023

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Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.

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Section: Amino Acid Metabolismmentioning

confidence: 91%

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

et al. 2023

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“…Moreover, BCKDK overexpression promotes ovarian cancer cell proliferation and migration by inducing the MEK/ERK pathway. Accordingly, BCKDK knockdown with shRNAs repressed ovarian cancer cell proliferation and migration in vivo and ex vivo ( 71 ). Transfection of anti- BCKDK siRNA into non-small cell lung cancer cells, including A549, HCC827, and H1299, reduced the expression of BCKDK, decreased BCKDE1α phosphorylation, and inhibited the proliferation of tumor cells in these cancers.…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions

Xu,

Ji,

Jin

et al. 2023

Front. Oncol.

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Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.

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“…BCKDK can affect tumorigenesis 6 and distant metastasis 7 in colorectal cancer by regulating the MEK/ERK signaling pathway. BCKDK can promote tumor proliferation and migration in ovarian cancer by activating the MEK/ERK axis 8 . BCKDK knockout in non‐small cell lung cancer can inhibit cancer cell proliferation and accelerate apoptosis 9 .…”

Section: Introductionmentioning

confidence: 99%

“…BCKDK can promote tumor proliferation and migration in ovarian cancer by activating the MEK/ERK axis. 8 BCKDK knockout in non‐small cell lung cancer can inhibit cancer cell proliferation and accelerate apoptosis. 9 Inhibiting BCKDK can increase the cytotoxicity of doxorubicin in triple‐negative breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Branched‐chain keto‐acid dehydrogenase kinase regulates vascular permeability and angiogenesis to facilitate tumor metastasis in renal cell carcinoma

Yang,

Xu,

Sun

et al. 2023

Cancer Science

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Branched‐chain keto‐acid dehydrogenase kinase (BCKDK) is the rate‐limiting enzyme of branched‐chain amino acid (BCAA) metabolism. In the last six years, BCKDK has been used as a kinase to promote tumor proliferation and metastasis. Renal cell carcinoma (RCC) is a highly vascularized tumor. A high degree of vascularization promotes tumor metastasis. Our objective is to explore the relationship between BCKDK and RCC metastasis and its specific mechanism. In our study, BCKDK is highly expressed in renal clear cell carcinoma and promotes the migration of clear cell renal cell carcinoma (ccRCC). Exosomes from ccRCC cells can promote vascular permeability and angiogenesis, especially when BCKDK is overexpressed in ccRCC cells. BCKDK can also augment the miR‐125a‐5p expression in ccRCC cells and derived exosomes, thereby decreasing the downstream target protein VE‐cadherin level, weakening adhesion junction expression, increasing vascular permeability, and promoting angiogenesis in HUVECs. The novel BCKDK/Exosome‐miR‐125a‐5p/VE‐cadherin axis regulates intercellular communication between ccRCC cells and HUVECs. BCKDK plays a critical role in renal cancer metastasis, may be used as a molecular marker of metastatic ccRCC, and even may become a potential target of clinical anti‐vascular therapy for ccRCC.

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BCKDK Promotes Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway

Cited by 7 publications

References 58 publications

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions

Branched‐chain keto‐acid dehydrogenase kinase regulates vascular permeability and angiogenesis to facilitate tumor metastasis in renal cell carcinoma

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