Mitochondria and Cancer 線粒體和癌症

by Alexandr V. Bazhin 1,21 Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians University, 81377 Munich, Germany 2 German Cancer Consortium (DKTK), Partner Site Munich, 80336 Munich, Germany Cancers 2020, 12(9), 2641; https://doi.org/10.3390/cancers12092641 Received: 7 September 2020 / Accepted: 9 September 2020 / Published: 16 September 2020 (This article belongs to the Special Issue Mitochondria and Cancer)
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Mitochondria are indispensable for energy metabolism and are essential for the regulation of many cellular processes in healthy as well as in transformed cells. Mitochondria in malignant cells differ structurally and functionally from those in normal cells, which make them a promising target for anticancer therapy.

Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression and participating in signaling pathways.

Additionally, the pleiotropic roles of mitochondrial ROS in the regulation of anticancer immunity are now coming to light. The involvement of mitochondria in cancer cell metabolic reprogramming as well as in the anticancer immune response has been utilized for designing novel mitochondria-targeted anticancer agents.

However, we are still far from an in depth understanding of the role played by mitochondria in cancer development. Therefore, the main aim of this Special Issue was to collect novel findings and ideas from scientists involved in basic research as well as in translational studies in the field of mitochondria and cancer.

Hguen and Pandey [1] discussed profoundly in their review “Expoiting Mitochondrial Vulnerability to trigger Apoptosis Selectively in Cancer Cells” regarding recent mitochondrial-selective anticancer compounds with efficient toxicity against cancer cells. These compounds should create a vicious cycle of mitohondrial dysfunction leading to the production of reactive oxygen species (ROS) and finally to cell suicide.

Furthermore, the authors conceptualized a possibility of the combination of these compounds for therapeutic usage.Another interesting point in gender-related anticancer treatment is the topic of the review of Stakisaitis et al.: “The Importance of Gender-Related Anticancer Research on Mitochondrial regulator Sodium Dichloroacetate in Preclinical Studies In Vivo” [2]. The review describes an excellent example of such gender-related effect by cancer treatment with sodium dichloroacetate. The authors conclude that gender-related differences in pharmacology of drugs targeting cancer mitochondrion should be recognized especially in the context of an individualized therapy.

Jeena et al. [3] hypothesized in their paper “Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy” that certain structural differences in mitochondria between normal and cancer cells could be used for the designing of selective anticancer drugs. In respect of this assumption, the authors give us an overview about alternative drug-free approaches to target cancer mitochondria. The discussed approaches may open new avenues for unconventional strategies to combat cancer.

Autophagy is a key node for the regulation of ROS levels as well as for the ROS-dependent cellular regulation. Therefore, such regulation could be a potential target mechanism for cancer treatment. Based on this idea, Sanches-Ávarez et al. [4] recognize the sestrin family of proteins as a “missing link” between ROS and autophagy in cancer cells. In their review “Sestrins as a Therapeutic bridge between ROS and Autophagy in Cancer”, the authors discuss possibilities for the adaptive regulation of ROS-induced autophagy by sestrins. Finally, they propose synergistic strategies using the pharmacological regulation of these proteins for personalized anticancer therapy.

The drug resistance, without question, is a huge barrier in the struggle against cancer. As previously mentioned, it is important to know the structural differences between normal and cancer cells. Moscheni et al. [5] also contemplated in the same way and investigated in their work “3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells” the differences in the mitochondrial morphology in drug-resistant cells against drug-sensitive ones using the soft X-ray cryo nanotomography. Indeed, they found certain differences in the cell strains. It is certain that these data will be helpful for designing new anticancer strategies.

Finally, Meng et al. [6] in their research article “Oncogenic K-ras Induces Mitochondrial OPA3 Expression to promote Energy metabolism in Pancreatic Cancer Cells” present evidence that OPA3 might be involved in cellular energy metabolism, and its upregulation has a link to K-ras mutations. Such upregulation finally led to the modulation of cancer cell proliferation and of epithelial–mesenchymal transition. These data are important considering that pancreatic cancer is one of the deadliest cancers in the world.

Summarizing, a small but high quality spectrum of reviews and original papers from this issue provides an insight into new research directions linked to an extremely important topic “Mitochondria and Cancer”. I hope all readers of this Special Issue enjoy taking a closer look into a subject of this compendium.

線粒體對於能量代謝是必不可少的,並且對於調節健康細胞和轉化細胞中的許多細胞過程至關重要。惡性細胞中的線粒體在結構和功能上與正常細胞不同,這使它們成為抗癌治療的有希望的靶點。

癌細胞中的線粒體以活性氧 (ROS) 過量產生為特徵,它通過誘導基因組不穩定性、改變基因表達和參與信號通路促進癌症發展。

此外,線粒體 ROS 在抗癌免疫調節中的多效作用現在逐漸浮出水面。線粒體參與癌細胞代謝重編程以及抗癌免疫反應已被用於設計新型線粒體靶向抗癌劑。

然而,我們還遠未深入了解線粒體在癌症發展中所起的作用。因此,本期特刊的主要目的是收集參與線粒體和癌症領域基礎研究以及轉化研究的科學家的新發現和想法。

Hguen 和 Pandey [1] 在他們的評論“利用線粒體脆弱性觸發癌細胞選擇性凋亡”中深入討論了最近對癌細胞具有有效毒性的線粒體選擇性抗癌化合物。這些化合物會造成線粒體功能障礙的惡性循環,導致產生活性氧 (ROS) 並最終導致細胞自殺。

此外,作者概念化了將這些化合物組合用於治療用途的可能性。性別相關抗癌治療的另一個有趣點是 Stakisaitis 等人的評論主題:“性別相關抗癌研究對線粒體調節劑的重要性體內臨床前研究中的二氯乙酸鈉”[2]。這篇綜述描述了用二氯乙酸鈉治療癌症的這種性別相關效應的一個很好的例子。作者得出結論,特別是在個體化治療的背景下,應認識到靶向癌症線粒體的藥物藥理學方面的性別相關差異。

吉娜等人。 [3] 在他們的論文“用於癌症治療的線粒體靶向藥物和無藥物藥物的最新進展”中假設,正常細胞和癌細胞之間線粒體的某些結構差異可用於設計選擇性抗癌藥物。關於這一假設,作者向我們概述了靶向癌症線粒體的替代無藥物方法。所討論的方法可能為非傳統的抗癌策略開闢新的途徑。

自噬是調節 ROS 水平以及 ROS 依賴性細胞調節的關鍵節點。因此,這種調節可能是癌症治療的潛在靶點機制。基於這個想法,Sanches-Ávarez 等人。 [4] 將 sestrin 蛋白家族識別為癌細胞中 ROS 和自噬之間的“缺失環節”。在他們的評論“Sestrins 作為癌症中 ROS 和自噬之間的治療橋樑”中,作者討論了 sestrins 對 ROS 誘導的自噬進行適應性調節的可能性。最後,他們提出了利用這些蛋白質的藥理學調節的協同策略,用於個性化抗癌治療。

毫無疑問,耐藥性是抗擊癌症的巨大障礙。如前所述,了解正常細胞和癌細胞之間的結構差異很重要。莫舍尼等人。 [5] 也以同樣的方式考慮並在他們的工作“3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells”中研究了耐藥細胞對藥物敏感的線粒體形態的差異那些使用軟 X 射線冷凍納米斷層掃描。事實上,他們發現細胞株存在某些差異。可以肯定的是,這些數據將有助於設計新的抗癌策略。

最後,孟等人。 [6] 在他們的研究文章“致癌 K-ras 誘導線粒體 OPA3 表達以促進胰腺癌細胞的能量代謝”中提出證據表明 OPA3 可能參與細胞能量代謝,其上調與 K-ras 突變有關。這種上調最終導致癌細胞增殖和上皮間質轉化的調節。考慮到胰腺癌是世界上最致命的癌症之一,這些數據很重要。

總而言之,來自本期的少量但高質量的評論和原始論文提供了對與極其重要的主題“線粒體和癌症”相關的新研究方向的洞察。

Funding

This research received no external funding.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Nguen, C.; Pandey, S. Exploiting Mitochondrial Vulnerabilities to Trigger Apoptosis Selectively in Cancer Cells. Cancers 2019, 11, 916. [Google Scholar]
  2. Stakisaitis, D.; Jukneviciene, M.; Damanskiene, E.; Valanciute, A.; Balnyte, I.; Alonso, M.M. The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo. Cancers 2019, 11, 1210. [Google Scholar]
  3. Jeena, M.T.; Kim, S.; Jin, S.; Ryu, J.-H. Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy. Cancers 2020, 12, 4. [Google Scholar]
  4. Sánchez-Álvarez, M.; Strippoli, R.; Donadelli, M.; Bazhin, A.V.; Cordani, M. Sestrins as a Therapeutic Bridge between ROS and Autophagy in Cancer. Cancers 2019, 11, 1415. [Google Scholar]
  5. Moscheni, C.; Malucelli, E.; Castiglioni, S.; Procopio, A.; De Palma, C.; Sorrentino, A.; Sartori, P.; Locatelli, L.; Pereiro, E.; Maier, J. 3D Quantitative and Ultrastructural Analysis of Mitochondria in a Model of Doxorubicin Sensitive and Resistant Human Colon Carcinoma Cells. Cancers 2019, 11, 1254. [Google Scholar]
  6. Meng, N.; Glorieux, C.; Zhang, Y.; Liang, L.; Zeng, P.; Lu, W.; Huang, P. Oncogenic K-ras Induces Mitochondrial OPA3 Expression to Promote Energy Metabolism in Pancreatic Cancer Cells. Cancers 2020, 12, 65. [Google Scholar]

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