Interplay Between Primary Cilia and Autophagy and Its Controversial Roles in Cancer

Ko, Je Yeong; Lee, Eun Ji

doi:10.4062/biomolther.2019.056

Cited by 13 publications

(11 citation statements)

References 67 publications

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“…Our preliminary results show that SANFH is associated with autophagy, and the autophagy‐related Beclin 1 and microtubule‐associated protein 1 light chain 3 (MAP1LC3) are upregulated in osteoblasts. Primary cilia are sensitive cellular antennae that sense and transmit external signals, and coordinate the responsive mechanisms. Recent studies show that the formation of primary cilia depends on autophagy.…”

Section: Introductionmentioning

confidence: 84%

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

Zhao

Liu

Guo

et al. 2020

Orthopaedic Surgery

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Objective: To study the role of primary cilia formation disorder and osteoblasts autophagy in the pathogenesis of steroid-induced avascular necrosis of the femoral head (SANFH).Methods: Osteoblasts were isolated from rabbit bones and treated with 1 μM Methylprednisolone for 0, 12, 24, 48, and 72 h. The Beclin1, MAP1LC3, Atg-5, Atg-12, IFT20 and OFD1 mRNAs and proteins were detected by PCR and Western blotting, and their correlation was statistically analyzed. The lengths of osteoblast cilia were measured under a laser confocal microscope, and the autophagy flux was tracked by transfecting the osteoblasts with GFP-RFP-LC3 lentivirus.Results: Methylprednisolone significantly upregulated Beclin1, MAP1LC3, Atg-5, Atg-12 and OFD1 mRNAs and proteins in a time-dependent manner, and decreased that of IFT20 (P < 0.05). In addition, the autophagy flux in the osteoblasts also increased and the ciliary length decreased in a time-dependent manner after Methylprednisolone treatment. The length of the cilia were 5.46 AE 0.11 um at 0 h, 4.08 AE 0.09 um at 12 h, 3.07 AE 0.07 um at 24 h, 2.31 AE 0.10 um at 48 h, and finally 1.15 AE 0.04 um at 72 h. Methylprednisolone treatment also affects primary cilium numbers in cultures, for 0 to 72 h. The autophagy regulatory genes, Beclin1, MAP1LC3, Atg-5 and Atg-12, were found to be negatively correlated with IFT20, with an average correlation coefficient of −0.81. A negative correlation was also found between OFD1 and IFT20, with an average correlation coefficient of −0.53. Conclusion:Methylprednisolone inhibits primary cilia formation and promotes autophagy, which could be the pathological basis of SANFH. The exact regulatory mechanism needs to be further studied in vivo.

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Section: Introductionmentioning

confidence: 84%

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

Zhao

Liu

Guo

et al. 2020

Orthopaedic Surgery

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“…Besides, drugs targeting autophagy combined with rapamycin, has been recently shown a therapeutic effect, suggesting a new therapeutic target for the disease (Zhu et al, 2017). Multiple cancers, including breast cancer and renal cell carcinoma, are the other disease models which have been studied concerning the interplay between ciliogenesis and autophagy Menzl et al, 2014;Ko et al, 2019). Cilia is known to be hardly detected in many cancer cells, whereas the role of autophagy is considered as the double-edged sword in cancer progression until now (Amaravadi et al, 2019;Romero et al, 2019;Yang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

The Autophagy Regulator p62 Controls PTEN-Dependent Ciliogenesis

Mun

Lee

Park

et al. 2020

Front. Cell Dev. Biol.

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Autophagy is a catabolic process required for maintaining intracellular energy homeostasis. It eliminates harmful proteins and recycles functional macromolecules back into the cell via cargo breakdown. Autophagy is generally suppressed under fed conditions and induced by serum starvation; therefore, it is considered to be a nutrientsensing mechanism. Cilia, finger-like organelles harboring multiple receptors along their surface, are energy-sensing structures that are also triggered by serum deprivation. Herein, we verified the effect of autophagy alterations on cilia assembly and the specific underlying mechanisms. Autophagy flux altered either by drugs or autophagy-targeting siRNAs strongly inhibited ciliogenesis, and this inhibition was affected by p62, an autophagy regulator, via Pten/Dvl2/AurKA signaling.

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“…This further implies that Caveolin-1 has a role in the metastatic process, as evidenced by increased migration, invasion and anchorage-independent growth (255). Furthermore, recent studies have unveiled the existence of an interplay between the primary cilium and autophagy in the regulation of cancer development and progression (256)(257)(258). In addition to being considered as a survival mechanism in tumorigenesis, excessive accumulation of autophagosomes may induce autophagic cell death or apoptosis (259)(260)(261)(262), which, in the context of cancer, limits tumor growth and spread.…”

Section: Mechanics Of Autophagy During Cancer Transformationmentioning

confidence: 99%

Mechanobiology of Autophagy: The Unexplored Side of Cancer

et al. 2021

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Proper execution of cellular function, maintenance of cellular homeostasis and cell survival depend on functional integration of cellular processes and correct orchestration of cellular responses to stresses. Cancer transformation is a common negative consequence of mismanagement of coordinated response by the cell. In this scenario, by maintaining the balance among synthesis, degradation, and recycling of cytosolic components including proteins, lipids, and organelles the process of autophagy plays a central role. Several environmental stresses activate autophagy, among those hypoxia, DNA damage, inflammation, and metabolic challenges such as starvation. In addition to these chemical challenges, there is a requirement for cells to cope with mechanical stresses stemming from their microenvironment. Cells accomplish this task by activating an intrinsic mechanical response mediated by cytoskeleton active processes and through mechanosensitive protein complexes which interface the cells with their mechano-environment. Despite autophagy and cell mechanics being known to play crucial transforming roles during oncogenesis and malignant progression their interplay is largely overlooked. In this review, we highlight the role of physical forces in autophagy regulation and their potential implications in both physiological as well as pathological conditions. By taking a mechanical perspective, we wish to stimulate novel questions to further the investigation of the mechanical requirements of autophagy and appreciate the extent to which mechanical signals affect this process.

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Interplay Between Primary Cilia and Autophagy and Its Controversial Roles in Cancer

Cited by 13 publications

References 67 publications

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

The Autophagy Regulator p62 Controls PTEN-Dependent Ciliogenesis

Mechanobiology of Autophagy: The Unexplored Side of Cancer

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