Taking out the JNK: A window of opportunity to improve cancer therapy

Ferrão, Paulo

doi:10.1080/23723556.2015.1128515

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…However, based on the findings in Drosophila tumour models described here and previously [ 71 , 72 , 90 , 100 ], inhibiting JNK signalling may restore differentiation and suppress the malignant overgrowth and invasive characteristics in many human tumours. Indeed, in bRAF (b-RAF proto-oncogene)-driven melanomas, JNK-cJun (cellular-Jun proto-oncogene) signalling has been revealed to contribute to tumour progression, suggesting that blocking JNK signalling may be of therapeutic benefit in at least some cancer types [ 124 , 125 , 126 ]. However, although JNK clearly plays an important role in Src + Ras ACT tumourigenesis, the activation of JNK signalling with Ras ACT does not result in as aggressive tumours as with Src + Ras ACT [ 51 ], which might be due to the contribution of Src signalling to Hippo pathway impairment [ 44 ] or to possible effects of Src on the activation of Myosin II activity and actinomyosin cell contractility, cell shape changes and tissue growth [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

Poon

Brumby

Richardson

2018

IJMS

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The Ras oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a Drosophila melanogaster genetic screen for genes that cooperate with oncogenic Ras (bearing the RasV12 mutation, or RasACT), we identified the Drosophila Src (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, Src42A and Src64B, as promoting increased hyperplasia in a whole epithelial tissue context in the Drosophila eye. Moreover, overexpression of Src cooperated with RasACT in epithelial cell clones to drive neoplastic tumourigenesis. We found that Src overexpression alone activated the Jun N-terminal Kinase (JNK) signalling pathway to promote actin cytoskeletal and cell polarity defects and drive apoptosis, whereas, in cooperation with RasACT, JNK led to a loss of differentiation and an invasive phenotype. Src + RasACT cooperative tumourigenesis was dependent on JNK as well as Phosphoinositide 3-Kinase (PI3K) signalling, suggesting that targeting these pathways might provide novel therapeutic opportunities in cancers dependent on Src and Ras signalling.

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Section: Discussionmentioning

confidence: 99%

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

Poon

Brumby

Richardson

2018

IJMS

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“…Therefore, in order to look for potential therapeutic targets of chemotherapy resistance to improve the effect of treatment, many researches focused on studying the mechanism of chemotherapy drug resistance. The activation of the JNK signaling pathway plays an important role in promoting drug resistance in cancer [90, 91]. Furthermore, there are also many researches reporting that c-jun is overexpressed in cisplatin resistance in ovarian cancer tissue [34].…”

Section: The Role Of Jnk Pathway In Chemotherapy Resistancementioning

confidence: 99%

The Jun N-terminal kinases signaling pathway plays a “seesaw” role in ovarian carcinoma: a molecular aspect

et al. 2019

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Ovarian cancer is the most common gynecological malignancy that causes cancer-related deaths in women today; this being the case, developing an understanding of ovarian cancer has become one of the major driving forces behind cancer research overall. Moreover, such research over the last 20 years has shown that the Jun N-terminal kinase (JNK) signaling pathway plays an important role in regulating cell death, survival, growth and proliferation in the mitogen-activated protein kinases (MAPK) signaling pathway, an important pathway in the formation of cancer. Furthermore, the JNK signaling pathway is often regulated by an abnormal activation in human tumors and is frequently reported in the literature for its effect on the progression of ovarian cancer. Although the FDA has approved some JNK inhibitors for melanoma, the agency has not approved JNK inhibitors for ovarian cancer. However, there are some experimental data on inhibitors and activators of the JNK signaling pathway in ovarian cancer, but related clinical trials need to be further improved. Although the Jun N-terminal kinase (JNK) signaling pathway is implicated in the formation of cancer in general, research has also indicated that it has a role in suppressing cancer as well. Here, we summarize this seemingly contradictory role of the JNK signaling pathway in ovarian cancer, that 'seesaws' between promoting and suppressing cancer, as well as summarizing the application of several JNK pathway inhibitors in cancer in general, and ovarian cancer in particular.

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“…One example of a newly developed drug from cancer research is MPT0G066, which induces JNK activation, influencing cell cycle regulatory and Bcl -2 family proteins, which triggers intrinsic apoptotic pathways. Adriamycin resulted in a timeand dose-dependent activation of JNK and treatment with vinblastine, or etoposide (VP-16) also activated JNK [66][67][68].…”

Section: Drugs Targeting Tor and Jnkmentioning

confidence: 99%

Co-evolutionary analysis of the immune and nervous systems may reveal novel diagnosis and treatment options for mental health and neurodegenerative disorders

Cunha¹

2019

Preprint

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Theories regarding the co-evolution of the immune system and neuronal network have been discussed throughout science history, but only recently research has shown evidence of the immune system modulating the neuronal circuitry of social behavior directly. Targeting the communication of the two systems would be an important novel approach that holds the potential for discoveries and development of precise diagnosis and treatments, and possibly even prevention of illnesses such as Parkinson, Alzheimer, and autism. We hypothesize, that there are 3 ways for the system to be dysregulated in pathologies: 1) the neuronal network is mal-functioning by default and derails the immune system, 2) basically vice versa and both, 3) the immune system gets triggered too early too much or chronically (inflammation, pollution, stress, etc), which then leads to aberrations of the central nervous system and its behavioral responses, however, even in this scenario some organisms cope with chronic stressors, displaying resilience, and others don’t. We hypothesize, that downregulation or blockage of immune-neuronal network communication would be an important target for treatment or even prevention of various illnesses, including neurological and mental health disorders. We will discuss various mechanisms supporting this co-evolution hypothesis, including cytokines modulating behavior and neurotransmitters modifying immune responses, and novel targets that could be potentially utilized for novel treatment development. In the light of fast increasing rate of mental health and neurological illnesses, we need to establish the risk level in individuals for aberrant immune-neuronal system/communication-related disorders development, which will play an important role in sustaining stable public health and therefore also a steady economy. In the future, the development of novel screening and analyzing technology will lead to cost-effectiveness, enabling us to utilize these individualized preventive screenings as broadly applied tools.

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Taking out the JNK: A window of opportunity to improve cancer therapy

Cited by 4 publications

References 10 publications

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

The Jun N-terminal kinases signaling pathway plays a “seesaw” role in ovarian carcinoma: a molecular aspect

Co-evolutionary analysis of the immune and nervous systems may reveal novel diagnosis and treatment options for mental health and neurodegenerative disorders

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