Cancer cells exploit adaptive mitochondrial dynamics to increase tumor cell invasion

Caino, M. Cecilia; Altieri, Dario C.

doi:10.1080/15384101.2015.1084448

Cited by 31 publications

(26 citation statements)

References 57 publications

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“…In fact, cancer cells frequently show an imbalance of fission and fusion. Accumulating evidence is beginning to provide an increased mechanistic understanding of how mitochondrial dynamics, which reflect the organelles’ exquisite heterogeneity in shape and spatial distribution, affect tumorigenesis and participate in metabolic reprogramming . Consistent with these observations, many studies have shown that the mitochondria‐associated fission protein Drp1 promotes tumor migration and pathogenesis, including in lung cancer, metastatic breast cancer, glioblastoma, colorectal cancer, pancreatic cancers, thyroid tumors, nasopharyngeal carcinoma and melanoma (Table ).…”

Section: Mitochondrial Network Structure Imbalance Is Associated Withmentioning

confidence: 89%

Mitochondrial network structure homeostasis and cell death

et al. 2018

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Mitochondria are the major cellular energy‐producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin‐related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach.

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Section: Mitochondrial Network Structure Imbalance Is Associated Withmentioning

confidence: 89%

Mitochondrial network structure homeostasis and cell death

et al. 2018

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“…With the vastly different oncogenic phenotypes of the Her2 and PyMT models, it seems logical that mitochondrial effects on tumorigenesis and metastasis are dependent upon the driver(s) present. Recent studies from the Altieri lab implicate mitochondrial localization as a key regulator of the metastatic phenotype (40, 47, 48). Coordination of mitochondrial position requires interactions between these organelles and other cytoplasmic (nuclear-encoded) structures, further highlighting mitochondrial-nuclear cross-talk.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

et al. 2017

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Using a novel mouse model, a mitochondrial-nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA with either FVB/NJ, C57BL/6J, or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ mitochondrial genome (i.e., females crossed with Her2 males) showed significantly (P < 0.001) longer tumor latency (262 vs. 293 vs. 225 days), fewer pulmonary metastases (5 vs. 7 vs. 15), and differences in size of lung metastases (1.2 vs. 1.4 vs. 1.0 mm diameter) compared with FVB/NJ mtDNA. Although polyoma virus middle T–driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. Collectively, these results establish mitochondrial polymorphisms as quantitative trait loci in mammary carcinogenesis, and they implicate distinct interactions between tumor drivers and mitochondria as critical modifiers of tumorigenicity and metastasis.

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“…In all cases, this reduction of mitochondria to the vicinity of FAs was associated with impaired focal adhesion dynamics and tumor cell invasion when compared with OxPhos‐proficient (wild type [WT]) cells or vehicle‐treated cells. Overall, these studies suggest that only bioenergetically active mitochondria travel to the cortical cytoskeleton and localize to FAs . These cortical mitochondria might support enhanced cell motility and invasion by numerous mechanisms (Figure ), including providing a local source of energy (ATP and guanosine triphosphate [GTP]) to fuel signal transduction and cytoskeleton dynamics at the leading edge.…”

Section: Mitochondrial Localization Impacts Cellular Functionmentioning

confidence: 99%

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

Furnish

Caino

2019

Cancer Reports

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Background Mammalian cells must constantly reprogram the distribution of mitochondria in order to meet the local demands for energy, calcium, redox balance, and other mitochondrial functions. Mitochondrial localization inside the cell is a result of a combination of movement along the microtubule tracks plus anchoring to actin filaments. Recent findings Recent advances show that subcellular distribution of mitochondria can regulate tumor cell growth, proliferation/motility plasticity, metastatic competence, and therapy responses in tumors. In this review, we discuss our current understanding of the mechanisms by which mitochondrial subcellular distribution is regulated in tumor cells. Conclusions Mitochondrial trafficking is dysregulated in tumors. Accumulation of mitochondria at the leading edge of the cell supports energy expensive processes of focal adhesion dynamics, cell membrane dynamics, migration, and invasion.

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Cancer cells exploit adaptive mitochondrial dynamics to increase tumor cell invasion

Cited by 31 publications

References 57 publications

Mitochondrial network structure homeostasis and cell death

Mitochondrial network structure homeostasis and cell death

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

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