PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation

Liu, Bo; Yao, Xueting; Zhang, Chaoyang; Yu-fen, Liu; Li, Wei; Huang, Qinying; Wang, Mengting; Zhang, Yanchen; Hu, Dan‐Ning; Wu, Wencan

doi:10.1038/s41419-023-05590-w

Cited by 10 publications

(11 citation statements)

References 64 publications

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“…PTK6, a member of the tyrosine kinase family, inhibits autophagy through the mTOR pathway, which further promotes the progression of UM. PTK6 is also highly expressed in UM samples and correlates with the prognosis of tumour patients, and experiments in nude mice have demonstrated that PTK6 promotes the growth of UM (Liu et al 2023b ). LINC01278 is lowly expressed in UM, and the tumour patients with high expression of LINC01278 have a better prognosis.…”

Section: Studies On Autophagy and Ummentioning

confidence: 99%

The multiple roles of autophagy in uveal melanoma and the microenvironment

Liu,

Yao,

Shang

et al. 2024

J Cancer Res Clin Oncol

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Purpose Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, and effective clinical treatment strategies are still lacking. Autophagy is a lysosome-dependent degradation system that can encapsulate abnormal proteins, damaged organelles. However, dysfunctional autophagy has multiple types and plays a complex role in tumorigenicity depending on many factors, such as tumor stage, microenvironment, signaling pathway activation, and application of autophagic drugs. Methods A systematic review of the literature was conducted to analyze the role of autophagy in UM, as well as describing the development of autophagic drugs and the link between autophagy and the tumor microenvironment. Results In this review, we summarize current research advances regarding the types of autophagy, the mechanisms of autophagy, the application of autophagy inhibitors or agonists, autophagy and the tumor microenvironment. Finally, we also discuss the relationship between autophagy and UM. Conclusion Understanding the molecular mechanisms of how autophagy differentially affects tumor progression may help to design better therapeutic regimens to prevent and treat UM.

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Section: Studies On Autophagy and Ummentioning

confidence: 99%

The multiple roles of autophagy in uveal melanoma and the microenvironment

Liu,

Yao,

Shang

et al. 2024

J Cancer Res Clin Oncol

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“…Although PTK6 has been explored in other cancers, its involvement in UM is yet to be fully elucidated. However, Liu et al reported that increased PTK6 expression in UM cells was associated with a poor prognosis [87]. Increased PTK6 activates mTOR and in turn, increases tumorigenesis by promoting the proliferation, migration, and invasion of UM cells and inhibiting autophagy [87].…”

Section: Protein Based Um Autophagy Biomarkersmentioning

confidence: 99%

“…However, Liu et al reported that increased PTK6 expression in UM cells was associated with a poor prognosis [87]. Increased PTK6 activates mTOR and in turn, increases tumorigenesis by promoting the proliferation, migration, and invasion of UM cells and inhibiting autophagy [87]. PTK6 binds to SOCS3 in UM cells, so that targeting the SOCS3-PTK6 signalling axis might be a novel and promising therapeutic strategy for patients with UM [87].…”

Section: Protein Based Um Autophagy Biomarkersmentioning

confidence: 99%

The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms

Wang,

Paulus,

Niu

et al. 2024

Biomedicines

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Autophagy is a form of programmed cell degradation that enables the maintenance of homeostasis in response to extracellular stress stimuli. Autophagy is primarily activated by starvation and mediates the degradation, removal, or recycling of cell cytoplasm, organelles, and intracellular components in eukaryotic cells. Autophagy is also involved in the pathogenesis of human diseases, including several cancers. Human uveal melanoma (UM) is the primary intraocular malignancy in adults and has an extremely poor prognosis; at present there are no effective therapies. Several studies have suggested that autophagy is important in UM. By understanding the mechanisms of activation of autophagy in UM it may be possible to develop biomarkers to provide more definitive disease prognoses and to identify potential drug targets for the development of new therapeutic strategies. This article reviews the current information regarding autophagy in UM that could facilitate biomarker and drug development.

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“…Since PTK6 activates STAT3 and STAT3 induces SOCS3 expression, this results in a negative feedback mechanism to control PTK6 activity [96]. A very recent study on uveal melanoma cells demonstrates that overexpression of SOCS3 can partially inhibit the PTK6-driven uveal melanoma cell proliferation [104].…”

Section: Biological Inhibitorsmentioning

confidence: 99%

Therapeutic Potential of Protein Tyrosine Kinase 6 in Colorectal Cancer

Jerin,

Harvey,

Lewis

2023

Cancers

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PTK6, a non-receptor tyrosine kinase, modulates the pathogenesis of breast and prostate cancers and is recognized as a biomarker of breast cancer prognosis. There are over 30 known substrates of PTK6, including signal transducers, transcription factors, and RNA-binding proteins. Many of these substrates are known drivers of other cancer types, such as colorectal cancer. Colon and rectal tumors also express higher levels of PTK6 than the normal intestine suggesting a potential role in tumorigenesis. However, the importance of PTK6 in colorectal cancer remains unclear. PTK6 inhibitors such as XMU-MP-2 and Tilfrinib have demonstrated potency and selectivity in breast cancer cells when used in combination with chemotherapy, indicating the potential for PTK6 targeted therapy in cancer. However, most of these inhibitors are yet to be tested in other cancer types. Here, we discuss the current understanding of the function of PTK6 in normal intestinal cells compared with colorectal cancer cells. We review existing PTK6 targeting therapeutics and explore the possibility of PTK6 inhibitory therapy for colorectal cancer.

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PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation

Cited by 10 publications

References 64 publications

The multiple roles of autophagy in uveal melanoma and the microenvironment

The multiple roles of autophagy in uveal melanoma and the microenvironment

The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms

Therapeutic Potential of Protein Tyrosine Kinase 6 in Colorectal Cancer

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