FOXM1-Induced PRX3 Regulates Stemness and Survival of Colon Cancer Cells via Maintenance of Mitochondrial Function

Song, In-Sung; Jeong, Yu Jeong; Jeong, Sang Hoon; Heo, Hye Jin; Kim, Hyoung Kyu; Bae, Ki Beom; Park, Young-Ho; Kim, Sun Uk; Kim, Jin Man; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

doi:10.1053/j.gastro.2015.06.007

Cited by 98 publications

(78 citation statements)

References 36 publications

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“…Prdx2 expression in stem cells differs in differentiated cells [44, 45]. A recent study revealed that Prdx3 was highly expressed in colon CSCs compared with non-CSCs [46]. In our study we found that Prdx2 was highly expressed in colon CSCs (CD133 + cells) compared with non-CSCs (CD133 - cells).…”

Section: Discussionsupporting

confidence: 58%

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Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

et al. 2016

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Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs. Prdx2 overexpression induced reversion of the self-renewal and sphere formation. Furthermore, the effects of Prdx2 resulted in an altered expression of stemness associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an effective therapeutic target for the elimination of CSCs in colorectal cancer.

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Section: Discussionsupporting

confidence: 58%

“…Prdx2 depletion attenuated stemness of CSCs in hepatocellular carcinoma [48]. Prdx3 depletion resulted in a smaller percentage of CD133 + cells, a significant reduction in sphere formation, and enhanced sensitivity to 5-FU [46]. Prdx4 plays the critical role for reducing oxidative stress in GSCs [49].…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

et al. 2016

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“…The role of PRDX3 in regulating cell growth has been widely studied in cancer cells3740. In colon cancer, PRDX3 was overexpressed in colon cancer stem cells and essential for maintenance of and survival of colon cancer stem cells41. Chua et al .…”

Section: Discussionmentioning

confidence: 99%

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Menon

et al. 2016

Sci Rep

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Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterised by raised bile acids in foetal-maternal circulation, which threatens perinatal health. During the progression of ICP, the effect of oxidative stress is underscored. Peroxiredoxin-3 (PRDX3) is a mitochondrial antioxidant enzyme that is crucial to balance intracellular oxidative stress. However, the role of PRDX3 in placental trophoblast cells under ICP is not fully understood. We demonstrated that the level of PRDX3 was downregulated in ICP placentas as well as bile acids–treated trophoblast cells and villous explant in vitro. Toxic levels of bile acids and PRDX3 knockdown induced oxidative stress and mitochondrial dysfunction in trophoblast cells. Moreover, silencing of PRDX3 in trophoblast cell line HTR8/SVneo induced growth arrest and cellular senescence via activation of p38-mitogen-activated protein kinase (MAPK) and induction of p21WAF1/CIP and p16INK4A. Additionally, enhanced cellular senescence, determined by senescence-associated beta-galactosidase staining, was obviously attenuated by p38-MAPK inhibitor SB203580. Our data determined that exposure to bile acid decreased PRDX3 level in human trophoblasts. PRDX3 protected trophoblast cells against mitochondrial dysfunction and cellular senescence induced by oxidative stress. Our results suggest that decreased PRDX3 by excessive bile acids in trophoblasts plays a critical role in the pathogenesis and progression of ICP.

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“…Prx3, member of the Trx2/TrxR2/Prx3 axis, is the major target of the H 2 O 2 generated in the mitochondrial matrix, and its inhibition has shown to sensitize cells to apoptosis 150 . Prx3's expression is upregulated in prostate 151 , colon 152 , and cervical 153 cancer, and some studies suggest it has an important role in the regulation of ROS-induced apoptosis in antiandrogen-resistant cells, which may convey its potential as a therapeutic target in prostate cancer 151 . Moreover, in a malignant mesothelioma cell line, it was established that Prx3 levels allowed cells to thrive in response to elevated mROS levels, and that any alteration in the redox activity of Prx3 impaired cell proliferation pausing the G2/M phase 154 , showing that this important peroxidase allows for proper cell cycle dynamics in this particular cancer cell line.…”

Section: Trx2/trxr2/prx3mentioning

confidence: 99%

Mitochondrial ROS control of cancer

Idelchik

Begley

et al. 2017

Seminars in Cancer Biology

239

169

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Mitochondria serve a primary role in energy maintenance but also function to govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have long been established to play a critical role in tumorigenesis and are now considered to be integral to the regulation of diverse signaling networks that drive proliferation, tumor cell survival and malignant progression. mROS can damage DNA, activate oncogenes, block the function of tumor suppressors and drive migratory signaling. The mitochondrion's oxidant scavenging systems including SOD2, Grx2, GPrx, Trx and TrxR are key of the cellular redox tone. These mitochondrial antioxidant systems serve to tightly control the levels of the primary ROS signaling species, H2O2. The coordinated control of mROS levels is also coupled to the activity of the primary H2O2 consuming enzymes of the mitochondria which are reliant on the epitranscriptomic control of selenocysteine incorporation. This review highlights the interplay between these many oncogenic signaling networks, mROS and the H2O2 emitting and consuming capacity of the mitochondria.

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FOXM1-Induced PRX3 Regulates Stemness and Survival of Colon Cancer Cells via Maintenance of Mitochondrial Function

Cited by 98 publications

References 36 publications

Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Mitochondrial ROS control of cancer

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