Modulation of Primary Cilia by Alvocidib Inhibition of CILK1

Wang, Elena X.; Turner, Jacob S.; Brautigan, David L.; Fu, Zheng

doi:10.3390/ijms23158121

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Primary cilia are present in various tissues throughout vertebrate development and act as cellular antennae to mediate cell signaling. Numerous ciliopathies are associated with defects in cilia length caused by deregulation of ciliary associated proteins ( 24 , 25 ). Accumulating evidence has confirmed the presence of primary cilia in developing and mature kidneys.…”

Section: Discussionmentioning

confidence: 99%

Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat

et al. 2023

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IntroductionIntrauterine malnutrition impairs embryo kidney development and leads to kidney disease and hypertension in adulthood, yet the underlying mechanism remains unclear.MethodsWith a maternal protein restriction (MPR) rat model, we investigated the critical ciliogenesis factors and β-catenin pathway in FGR fetal kidneys and analyzed the impact of aberrant primary cilia on renal tubular epithelium.ResultsThe data showed decreased nephron number and renal tubular dysgenesis in FGR fetus. FGR fetus showed deregulated expression of ciliogenesis factors including upregulation of IFT88 and downregulation of DYNLT1, accompanied with cilia elongation in renal tubular epithelial cells. Wnt7b, the key ligand for Wnt/β-catenin signaling, was downregulated and nuclear translocation of β-catenin was decreased. The proapoptotic protein was upregulated. In vitro study with HK-2 cells showed that overexpression of IFT88 lengthened the cilia, inhibited β-catenin signaling. Besides, IFT88 overexpression suppressed cell proliferation, activated autophagy, and induced cell apoptosis. Inhibition of autophagy partly restored the cilia length and cell viability. Likewise, knockdown of DYNLT1 led to cilia elongation, suppressed cell proliferation, and promoted apoptosis in HK-2 cell. However, the cilia elongation induced by DYNLT1 knockdown was not autophagy-dependent, but associated with reactive oxygen species (ROS) accumulation.DiscussionWe elucidated that intrauterine protein malnutrition led to deregulation of ciliogenesis factors and cilia elongation in renal tubular epithelial, inhibited β-catenin signaling, and induced cell apoptosis and ultimately, compromised kidney development.

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Section: Discussionmentioning

confidence: 99%

Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat

et al. 2023

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“…A proposed approach to target the PC is by the inhibition of ciliogenesis-associated kinase 1 (CILK1), a negative regulator of cilia length [180]. Alvocidib, a semi-synthetic flavone related to a natural product extracted from Indian plants, has been shown to be a potent inhibitor of CILK1 in cells, suggesting a potential use for targeting PCs in cancer [180].…”

Section: Implication Of Pc In Cancer Therapeuticsmentioning

confidence: 99%

Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies

Carotenuto

Gradilone

Franco

2023

Genes

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Cilia are microtubule-based organelles that project from the cell surface with motility or sensory functions. Primary cilia work as antennae to sense and transduce extracellular signals. Cilia critically control proliferation by mediating cell-extrinsic signals and by regulating cell cycle entry. Recent studies have shown that primary cilia and their associated proteins also function in autophagy and genome stability, which are important players in oncogenesis. Abnormal functions of primary cilia may contribute to oncogenesis. Indeed, defective cilia can either promote or suppress cancers, depending on the cancer-initiating mutation, and the presence or absence of primary cilia is associated with specific cancer types. Together, these findings suggest that primary cilia play important, but distinct roles in different cancer types, opening up a completely new avenue of research to understand the biology and treatment of cancers. In this review, we discuss the roles of primary cilia in promoting or inhibiting oncogenesis based on the known or predicted functions of cilia and cilia-associated proteins in several key processes and related clinical implications.

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Primary cilia shape hallmarks of health and aging

Silva¹,

Cavadas²

2023

Trends in Molecular Medicine

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Modulation of Primary Cilia by Alvocidib Inhibition of CILK1

Cited by 3 publications

References 35 publications

Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat

Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat

Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies

Primary cilia shape hallmarks of health and aging

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