TCTP as a therapeutic target in melanoma treatment

Bóia-Ferreira, Marianna; Basílio, Alana B.C.; Hamasaki, Azumi; Matsubara, Fernando Hitomi; Appel, Márcia Helena; Costa, Cleber Rafael Vieira da; Amson, Robert; Telerman, Adam; Chaim, Olga Meiri; Veiga, Sílvio Sanches; Senff‐Ribeiro, Andrea

doi:10.1038/bjc.2017.230

Cited by 25 publications

(30 citation statements)

References 32 publications

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“…For instance, it was reported that sertraline could induce ER calcium release in PC3 human prostate cancer cells ( 50 ). In addition, sertraline interacted with translationally controlled tumor protein and decreased its cellular levels, resulting in diminished migration properties and colony formation capacity of melanoma cells ( 51 ). Therefore, further experiments are needed to clarify whether these genes or pathways contributed to autophagy induction by sertraline.…”

Section: Discussionmentioning

confidence: 99%

Repurposing sertraline sensitizes non–small cell lung cancer cells to erlotinib by inducing autophagy

Jiang¹,

Lü²,

Shen³

et al. 2018

JCI Insight

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Lung cancer patients treated with tyrosine kinase inhibitors (TKIs) often develop resistance. More effective and safe therapeutic agents are urgently needed to overcome TKI resistance. Here, we propose a medical genetics–based approach to identify indications for over 1,000 US Food and Drug Administration–approved (FDA-approved) drugs with high accuracy. We identified a potentially novel indication for an approved antidepressant drug, sertraline, for the treatment of non–small cell lung cancer (NSCLC). We found that sertraline inhibits the viability of NSCLC cells and shows a synergy with erlotinib. Specifically, the cotreatment of sertraline and erlotinib effectively promotes autophagic flux in cells, as indicated by LC3-II accumulation and autolysosome formation. Mechanistic studies further reveal that dual treatment of sertraline and erlotinib reciprocally regulates the AMPK/mTOR pathway in NSCLC cells. The blockade of AMPK activation decreases the anticancer efficacy of either sertraline alone or the combination. Efficacy of this combination regimen is decreased by pharmacological inhibition of autophagy or genetic knockdown of ATG5 or Beclin 1. Importantly, our results suggest that sertraline and erlotinib combination suppress tumor growth and prolong mouse survival in an orthotopic NSCLC mouse model (P = 0.0005). In summary, our medical genetics–based approach facilitates discovery of new anticancer indications for FDA-approved drugs for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Repurposing sertraline sensitizes non–small cell lung cancer cells to erlotinib by inducing autophagy

Jiang¹,

Lü²,

Shen³

et al. 2018

JCI Insight

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“…Sertraline is now being tested in phase I/II clinical studies [101]. Recently, it was demonstrated that TCTP is a promising target in melanoma, also using sertraline as a drug [102]. In our initial experiments targeting TCTP, we employed anti-histaminic drugs [79].…”

Section: Mechanisms Of Cancer Promotion By Tctpmentioning

confidence: 99%

Dysregulation of TCTP in Biological Processes and Diseases

Bommer

Telerman

2020

Cells

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Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular defense in response to biological stresses. Cellular TCTP levels are highly regulated in response to a variety of physiological signals, and regulatory mechanism at various levels have been elucidated. Given the importance of TCTP in maintaining cellular homeostasis, it is not surprising that dysregulation of this protein is associated with a range of disease processes. Here, we review recent progress that has been made in the characterisation of the basic biological functions of TCTP, in the description of mechanisms involved in regulating its cellular levels and in the understanding of dysregulation of TCTP, as it occurs in disease processes such as cancer.

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“…Only scarce mixed preclinical data are available regarding a possible effect of AD on melanoma tumors. Whereas some studies suggested that certain ADs may be effective in inhibiting tumor growth in a murine model, have an in‐vitro cytotoxic activity against human melanoma cells or possess antioxidant activity in mice, other studies indicated that selective serotonin reuptake inhibitors may increase mice brain metastases or not affect them (Boia‐Ferreira et al, ; Herr, Mohile, van, Brown, & Rich, ). To the best of our knowledge, no clinical studies evaluated this question, which is particularly intriguing since melanocytes originate from the embryonic ectoderm, similarly to the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study

et al. 2019

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Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all‐cause mortality in a population‐based cohort of patients with cancer. Materials and Methods: We conducted a 4‐year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20–50%), moderate (50–80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality. Results: During 1,051,489 person‐years at risk follow‐up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83–0.95), 0.77 (95% CI: 0.66–0.72), and 0.80 (95% CI: 0.76–0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42–1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04–1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03–1.17]; P < .0001) and more physical comorbidities. Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all‐cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.

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TCTP as a therapeutic target in melanoma treatment

Cited by 25 publications

References 32 publications

Repurposing sertraline sensitizes non–small cell lung cancer cells to erlotinib by inducing autophagy

Repurposing sertraline sensitizes non–small cell lung cancer cells to erlotinib by inducing autophagy

Dysregulation of TCTP in Biological Processes and Diseases

Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study

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