Myoglobin induces mitochondrial fusion, thereby inhibiting breast cancer cell proliferation

Braganza, Andrea; Quesnelle, Kelly M.; Bickta, Janelle; Reyes, Christopher; Wang, Yinna; Jessup, Morgan; Croix, Claudette St.; Arlotti, Julie A.; Singh, Shivendra V.; Shiva, Sruti

doi:10.1074/jbc.ra118.006673

Cited by 28 publications

(40 citation statements)

References 51 publications

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“…Expression profiling of tumors from patients with head and neck squamous cell carcinoma has revealed that myoglobin expression is associated with better prognosis (Meller et al, 2016). The noncanonical tumor suppressor function of myoglobin has also been confirmed by preclinical investigations on breast cancer and lung cancer cells (Braganza et al, 2019;Galluzzo et al, 2009;Kristiansen et al, 2011).…”

Section: Discussionmentioning

confidence: 93%

Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

et al. 2020

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Section: Discussionmentioning

confidence: 93%

Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

et al. 2020

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“…As an alternative scenario to a p53-driven cell cycle arrest, oxy-MB was recently reported to decrease cell proliferation by inducing mitochondrial fusion in p53-wild-type, as well as in p53-gain-of-function-mutated and p53-loss-of-function-mutated cell lines (42). In this network, oxy-MB was described to produce ROS, which increased parkin oxidation and inhibited the degradation of mitofusin 1 and 2.…”

Section: Discussionmentioning

confidence: 99%

“…Only a limited number of hypothesis-driven experiments have been conducted thus far to elucidate the role of MB in cancer cells (28,41,42). The present study used the essentially unbiased approach of transcriptome analysis to reveal functional consequences of MB expression vs. RNAi-mediated MB knockdown in breast, prostate and colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The role of myoglobin in epithelial cancers: Insights from transcriptomics

et al. 2019

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The muscle-associated respiratory protein myoglobin (MB) is expressed in multiple types of cancer, including breast and prostate tumors. In Kaplan-Meier analyses of the two tumor types, MB positivity is associated with favorable prognoses. despite its well-characterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, small interfering RNA MB-knockdown cells were engineered using breast, prostate and colon cancer cell lines (MdA-MB468, LNcaP, dLd-1), and their transcriptomes were investigated using RNA-Seq at different oxygen levels. In MB-positive cells, increased expression of glycolytic genes was observed, which was possibly mediated by a higher activity of hypoxia-inducible factor 1α. In addition, the results of the gene set enrichment analysis suggested that MB contributed to fatty acid transport and turnover. MB-positive, wild-type-p53 LNcaP cells also exhibited increased expression of p53 target genes involved in cell cycle checkpoint control and prevention of cell migration. MB-positive cells expressing mutant p53 exhibited upregulation of genes associated with prolonged cancer cell viability and motility. Therefore, it was hypothesized that these transcriptomic differences may result from MB-mediated generation of nitric oxide or reactive oxygen species, thus employing established enzymatic activities of the globin. In summary, the transcriptome comparisons identified potential molecular functions of MB in carcinogenesis by highlighting the interaction of MB with key metabolic and regulatory processes.

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“…MFN1 and MFN2 are proteins localized at the outer mitochondrial membrane that promote mitochondrial fusion. Their upregulation thus leads to mitochondrial hyperfusion, which subsequently halts cell cycle progression at G1 to S phase transition [ 199 ]. Hence, Mb expression in cancer cells might attenuate cancer cell proliferation.…”

Section: Myoglobinmentioning

confidence: 99%

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

et al. 2020

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Vertebrate hemoglobin (Hb) and myoglobin (Mb) were among the first proteins whose structures and sequences were determined over 50 years ago. In the subsequent pregenomic period, numerous related proteins came to light in plants, invertebrates and bacteria, that shared the myoglobin fold, a signature sequence motif characteristic of a 3-on-3 α-helical sandwich. Concomitantly, eukaryote and bacterial globins with a truncated 2-on-2 α-helical fold were discovered. Genomic information over the last 20 years has dramatically expanded the list of known globins, demonstrating their existence in a limited number of archaeal genomes, a majority of bacterial genomes and an overwhelming majority of eukaryote genomes. In vertebrates, 6 additional globin types were identified, namely neuroglobin (Ngb), cytoglobin (Cygb), globin E (GbE), globin X (GbX), globin Y (GbY) and androglobin (Adgb). Furthermore, functions beyond the familiar oxygen transport and storage have been discovered within the vertebrate globin family, including NO metabolism, peroxidase activity, scavenging of free radicals, and signaling functions. The extension of the knowledge on globin functions suggests that the original roles of bacterial globins must have been enzymatic, involved in defense against NO toxicity, and perhaps also as sensors of O 2 , regulating taxis away or towards high O 2 concentrations. In this review, we aimed to discuss the evolution and remarkable functional diversity of vertebrate globins with particular focus on the variety of non-canonical expression sites of mammalian globins and their according impressive variability of atypical functions.

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Myoglobin induces mitochondrial fusion, thereby inhibiting breast cancer cell proliferation

Cited by 28 publications

References 51 publications

Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

The role of myoglobin in epithelial cancers: Insights from transcriptomics

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

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