Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism

Almeida, Nuno; Carrara, Guia; Palmeira, Carlos M.; Fernandes, Ana Sofia; Parsons, Maddy; Smith, Geoffrey L.; Saraiva, Nuno

doi:10.1016/j.redox.2019.101361

Cited by 17 publications

(17 citation statements)

References 70 publications

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“…Stage I and II survival rates were significantly higher than those for stage III and IV, which was consistent with previous studies (11). This difference might be related to tumor invasion and cell infiltration (12)(13)(14) improve the survival of colon cancer patients, it is necessary to focus on prevention and early detection and treatment.…”

Section: Discussionsupporting

confidence: 89%

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis

Pang

Lian

et al. 2022

Front. Oncol.

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The survival rate for colon cancer after radical surgery has been the focus of extensive debate. To assess the postoperative survival and prognostic factors for overall survival (OS), we collected clinicopathological information for 2,655 patients. The survival time and potential risk factors for OS were analyzed by using Kaplan–Meier curves, Cox proportional hazards models, best subset regression (BSR), and least absolute shrinkage and selection operator (LASSO). The 5-year survival rates of stage I–IV colon cancer were 96.6%, 88.7%, 69.9%, and 34.3%, respectively. Adjuvant chemotherapy improved the survival rate (90.4% vs. 82.4%, with versus without adjuvant chemotherapy, respectively) in stage II patients with high-risk factors. Elevated preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly associated with worse OS compared with patients without these elevations. Less than 12 versus more than 12 harvested lymph nodes (LNs) affected prognosis (84.6% vs. 89.7%, respectively). Regarding the lymph node ratio (LNR), the 5-year OS rate was 89.2%, 71.5%, 55.8%, and 34.5% in patients with LNR values of 0, 0.3, 0.3–0.7, and >0.7, respectively. We constructed a nomogram comprising the independent factors associated with survival to better predict prognosis. On the basis of these findings, we propose that stage II colon cancer patients without high-risk factors and with both elevated preoperative CEA and CA199 should receive adjuvant therapy. Furthermore, the LNR could complement TNM staging in patients with <12 harvested LNs. Our nomogram might be useful as a new prognosis prediction system for colon cancer patients.

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Section: Discussionsupporting

confidence: 89%

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis

Pang

Lian

et al. 2022

Front. Oncol.

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“…The six members of the TMBIM-protein family present in humans are evolutionarily conserved and have orthologues in viruses, prokaryotes, and virtually all eukaryotes. These proteins impact cellular Ca 2+ signaling, and they may function as ion-transport systems and control cell functions that promote survival, stress resilience, and cell migration [ 4 , 12 , 13 , 17 , 24 , 52 , 53 , 54 ]. In this study, we focused on TMBIM5, the only TMBIM-family member located at the inner mitochondrial membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Cells overexpressing TMBIM3 showed reduced apoptosis after treatment with hydrogen peroxide, and in zebrafish, its knockdown increased apoptosis [ 9 , 10 ]. TMBIM4, known also as Golgi Anti-Apoptotic Protein (GAAP), localizes in the ER and the Golgi apparatus and is expressed in all human tissues, and in addition to apoptosis, it also regulates cell adhesion and invasion [ 11 , 12 , 13 ]. TMBIM5 is a ubiquitously expressed mitochondrial family member that affects mitochondrial morphology and apoptosis [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery

Seitaj

Maull

Zhang

et al. 2020

Cells

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The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson’s disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.

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“…The produced H 2 O 2 also stimulates the PI3K/Akt pathway [ 30 , 40 ]. In addition to these signaling pathways, other H 2 O 2 -mediated mechanisms could be implicated in LOX effects since these reactive oxygen species have been shown to modulate other cancer progression-related events in different experimental models [ 41 , 42 , 43 ].…”

Section: Loxl2 and Cancermentioning

confidence: 99%

LOXL2 Inhibitors and Breast Cancer Progression

et al. 2021

Self Cite

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LOX (lysyl oxidase) and lysyl oxidase like-1-4 (LOXL 1-4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.

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Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism

Cited by 17 publications

References 70 publications

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis

Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery

LOXL2 Inhibitors and Breast Cancer Progression

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