Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

Grieco, Joseph P.; Allen, Mitchell E.; Perry, Justin B.; Wang, Yao; Song, Yipei; Rohani, Ali Haeri; Compton, Stephanie L. E.; Smyth, J. D.; Swami, Nathan S.; Brown, David A.; Schmelz, Eva M.

doi:10.3389/fonc.2020.600113

Cited by 36 publications

(55 citation statements)

References 95 publications

(153 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An example of a link between fragmented mitochondria and cancer was reported in mouse and human ovarian cancer cell lines, in which mitochondria changed with increasing malignancy from a filamentous network to single, rounded structures localized more closely adjacent to the nucleus, due to an imbalance of fusion and fission regulators. These changes aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, Δψ m , and ROS levels [ 156 ]. Similarly, in human invasive breast carcinoma, mitochondria were more fragmented in metastatic than in nonmetastatic cells, due to upregulation of DRP1 and downregulation of MFN1.…”

Section: General Features Of Mitochondrial Architecture In Cancer Cellsmentioning

confidence: 99%

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

Pedersen

Flinck

Pardo

2021

IJMS

View full text Add to dashboard Cite

Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and mitochondrial phenotype undergo pervasive changes during cancer development, and both play key roles in driving the malignancy. However, the link between these events has been largely ignored. This review comprehensively summarizes and critically discusses the role of the reciprocal relationship between ion transport and mitochondria in crucial cellular functions, including metabolism, signaling, and cell fate decisions. We focus on Ca2+, H+, and K+, which play essential and highly interconnected roles in mitochondrial function and are profoundly dysregulated in cancer. We describe the transport and roles of these ions in normal mitochondria, summarize the changes occurring during cancer development, and discuss how they might impact tumorigenesis.

show abstract

Section: General Features Of Mitochondrial Architecture In Cancer Cellsmentioning

confidence: 99%

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

Pedersen

Flinck

Pardo

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Mitochondria are tagged for degradation mainly when OXPHOS is compromised, which can be a consequence of the accumulation of ROS [39]. Oxidative stress is accrued when ROS levels surpass the capacity of antioxidant systems to remove ROS-a state often associated with hypoxia [40,41]. Mitophagy serves as such a mechanism to attenuate oxidative stress and reestablish redox homeostasis by reducing the production of ROS and the extent of oxidative damage [40,42].…”

Section: Metabolic Reprogramming As a Priming Mechanism In Response T...mentioning

confidence: 99%

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

Lee

Pena

Dawson

2022

Cancers

View full text Add to dashboard Cite

High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.

show abstract

“…Formerly, Grieco and coworkers reported changes in mitochondrial morphology with increasing malignity, namely, from network mitochondria to a single, enlarged mitochondrion in mouse ovarian surface epithelial (MOSE) cells [48]. The authors argue that these mitochondria changes may help adapt to hypoxia, and alterations accompany the modifications in the mitochondrial ultrastructure, mitochondrial membrane potential, and the adjustment of ROS levels [48]. Currently, mitochondria are proposed as one of the therapeutic targets to avoid chemoresistance [11,49].…”

Section: Tissue and Cell Linesmentioning

confidence: 99%

“…Additionally, a few isolated CSCs Formerly, Grieco and coworkers reported changes in mitochondrial morphology with increasing malignity, namely, from network mitochondria to a single, enlarged mitochondrion in mouse ovarian surface epithelial (MOSE) cells [48]. The authors argue that these mitochondria changes may help adapt to hypoxia, and alterations accompany the modifications in the mitochondrial ultrastructure, mitochondrial membrane potential, and the adjustment of ROS levels [48]. Currently, mitochondria are proposed as one of the therapeutic targets to avoid chemoresistance [11,49].…”

Section: Tissue and Cell Linesmentioning

confidence: 99%

“…The metabolic differences revealed that resistant cells to apoptosis undergo a shift toward OXPHOS [49]. Generally, the changes are accompanied by a reorganization in the mitochondrial network through increasing the mitochondrial ultrastructure [48]. The TME conditions with limited oxygen and glucose restrict metabolic plasticity in cancer cells, which has recently played a critical role in cancer progression and chemoresistance.…”

Section: Role Of Mitochondria In Chemoresistancementioning

confidence: 99%

See 1 more Smart Citation

Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer

Vera

Fredes

Garrido

et al. 2021

Life

View full text Add to dashboard Cite

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.

show abstract

Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

Cited by 36 publications

References 95 publications

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer

Contact Info

Product

Resources

About