The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3‐PHB2 complex formation

Toki, Shunichi; Yoshimaru, Tetsuro; Matsushita, Yosuke; Aihara, Hitoshi; Ono, M.; Tsuneyama, Koichi; Sairyo, Koichi; Katagiri, Toyomasa

doi:10.1111/cas.15099

Cited by 12 publications

(9 citation statements)

References 25 publications

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“…PHB2 also play an important role in the proliferation and survival of cancer cells through mitochondrial apoptosis [ 39 – 41 ], and down regulating the expression of PHB can significantly reduce the cell division rate [ 42 , 43 ]. Meanwhile, increasing evidence indicates that the PHB2-mediated signaling pathway is essential for the inhibition of cancer cell proliferation and migration [ 44 – 46 ].…”

Section: Resultsmentioning

confidence: 99%

Development of artesunate intelligent prodrug liposomes based on mitochondrial targeting strategy

Zhang

Liu

et al. 2022

J Nanobiotechnol

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Breast cancer is the leading cause of cancer-related deaths in women and remains a formidable therapeutic challenge. Mitochondria participate in a myriad of essential cellular processes, such as metabolism, and are becoming an ideal target for cancer therapy. Artemisinin and its derivatives have demonstrated multiple activities in the context of various cancers. Mitochondrial autophagy(mitophagy) is one of the important anti-tumor mechanisms of artemisinin drugs. However, the lack of specific tumor targeting ability limits the anti-tumor efficacy of artemisinin drugs. In this study, a GSH-sensitive artesunate smart conjugate (TPP-SS-ATS) was synthesized and liposomes (TPP-SS-ATS-LS) that target tumor cells and mitochondria were further prepared. The advantages of TPP-SS-ATS-LS targeting to the breast tumor were verified by in vivo and in vitro evaluations. In our study, the cytotoxicity was obviously enhanced in vitro and tumor growth inhibition rate was increased from 37.7% to 56.4% at equivalent artesunate dosage in breast cancer orthotopic implanted mice. Meanwhile, mitochondrial dysfunction, suppression of ATP production and respiratory capacity were detected in breast cancer cells. We further discovered that TPP-SS-ATS-LS inhibited tumor cells proliferation through mitophagy by regulating PHB2 and PINK1 expression. These results provide new research strategies for the development of new artemisinin-based anti-tumor drugs.

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Section: Resultsmentioning

confidence: 99%

Development of artesunate intelligent prodrug liposomes based on mitochondrial targeting strategy

Zhang

Liu

et al. 2022

J Nanobiotechnol

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“…By contrast, the analysis of publications argues against the direct involvement of Phb2 in the PTP/MMC complex formation. First, the Phb-Phb2 complex is essential for mitochondrial resistance to PTP and cell resistance to apoptotic stimuli [52,61,62]. Second, the Phb-Phb2 complex increases the stability of mitochondrial supercomplexes CI-CIII 2 -CIV x and CIII 2 -CIV n [63,64] and, most probably, F-ATP synthase oligomers through the stabilization of dynaminrelated GTPase OPA1 [65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Permeability transition pore-related changes in the proteome and channel activity of ATP synthase dimers and monomers

Nikiforova

Baburina

Borisova

et al. 2022

Preprint

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Monomers, dimers, and individual FOF1-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), which molecular structure, however, is still unknown. We hypothesized that upon the Ca2+-dependent assembly of PTP complex, F-ATP synthase (subunits) recruits mitochondrial proteins that do not interact or weakly interact with F-ATP synthase under normal conditions. Therefore, we examined whether the PTP opening in mitochondria before the separation of supercomplexes by BN-PAGE will increases the channel stability and channel-forming capacity of isolated F-ATP synthase dimers and monomers in planar lipid membranes. Besides, we studied the specific activity and protein composition of F-ATP synthase dimers and monomers from rat liver and heart mitochondria before and after PTP opening. By contrast to our expectations, preliminary PTP opening dramatically suppressed the high-conductance channel activity of F-ATP synthase dimers and monomers and decreased their specific "in gel" activity. The decline in the channel-forming activity correlated with the reduced levels of as few as two proteins in the bands: methylmalonate-semialdehyde dehydrogenase and prohibitin 2. These data indicate that proteins accompanying F-ATP synthase may be important players in the PTP formation and stabilization.

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“…In 2021, the Katagiri group extended the study of the BIG3-PHB2 interaction in osteosarcoma (OS). Much like breast cancer, overexpression of BIG3 was also discovered in OS [ 43 ]. Unlike breast cancer cells, however, the BIG3-PHB2 complex was found to be mainly localized in the mitochondria of OS cells.…”

Section: Phb2 Tumor Suppressor Functionmentioning

confidence: 99%

Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

Lamont

Liu

et al. 2023

Cells

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Prohibitins (PHBs) are a highly conserved class of proteins and have an essential role in transcription, epigenetic regulation, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism. Prohibitins form a heterodimeric complex, consisting of two proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2). They have been discovered to have crucial roles in regulating cancer and other metabolic diseases, functioning both together and independently. As there have been many previously published reviews on PHB1, this review focuses on the lesser studied prohibitin, PHB2. The role of PHB2 in cancer is controversial. In most human cancers, overexpressed PHB2 enhances tumor progression, while in some cancers, it suppresses tumor progression. In this review, we focus on (1) the history, family, and structure of prohibitins, (2) the essential location-dependent functions of PHB2, (3) dysfunction in cancer, and (4) the promising modulators to target PHB2. At the end, we discuss future directions and the clinical significance of this common essential gene in cancer.

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The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3‐PHB2 complex formation

Cited by 12 publications

References 25 publications

Development of artesunate intelligent prodrug liposomes based on mitochondrial targeting strategy

Development of artesunate intelligent prodrug liposomes based on mitochondrial targeting strategy

Permeability transition pore-related changes in the proteome and channel activity of ATP synthase dimers and monomers

Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

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