CDKL3 Targets ATG5 to Promote Carcinogenesis of Esophageal Squamous Cell Carcinoma

Zhou, Suna; Zhang, Mingxin; Zhou, Chao; Wang, Wei; Yang, Haihua; Ye, Wenguang

doi:10.3389/fonc.2020.01602

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…The exclusion criteria were: (1) Non-ESCC patients; (2) Without a completed postoperative report of pathological assessment;(3) Without enough samples stored in the tissue bank of Taizhou Hospital. The flow of immunohistochemical staining (IHC) was carried out as we described in the previous study ( 22 ). Two observers blinded to the purpose of the study independently evaluated the stained sections.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study analyzed the profile of differential expressed genes between KYSE-150-NC and KYSE-150-CDKL3-KD cells using GeneChip ® PrimeViewTM human gene expression arrays ( 22 ). In this study, we used IPA to perform gene enrichment analysis based on the results of CDKL3 expression-related differential gene expression.…”

Section: Methodsmentioning

confidence: 99%

“…Cyclin-dependent kinase-like 3 (CDKL3) is both a protein-coding gene and a member of the CDKL family ( 18 ). Existing research demonstrates that tumor patients with CDKL3 up-regulation are closely related to inferior survival status ( 19 – 22 ). Our previous study identified CDKL3 as an important oncogene in esophageal squamous cell carcinoma (ESCC) and autophagy-related gene ATG5 was a potential target of CDKL3 in KYSE-150 cell line ( 19 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

“…Existing research demonstrates that tumor patients with CDKL3 up-regulation are closely related to inferior survival status ( 19 – 22 ). Our previous study identified CDKL3 as an important oncogene in esophageal squamous cell carcinoma (ESCC) and autophagy-related gene ATG5 was a potential target of CDKL3 in KYSE-150 cell line ( 19 , 22 ). However, the effect of CDKL3 on TME and its role in autophagy are still unknown.…”

Section: Introductionmentioning

confidence: 99%

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CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

Bi,

Liu,

Qin

et al. 2024

Front. Immunol.

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BackgroundCDKL3 has been associated with the prognosis of several tumors. However, the potential role of CDKL3 in immunotherapy and the tumor microenvironment (TME) in esophageal carcinoma (ESCA) remains unclear.MethodsIn this study, Cox regression analysis was used to assess the predictive value of CDKL3 for ESCA outcomes. We systematically correlated CDKL3 with immunological features in the TME. The role of CDKL3 in predicting the efficacy of immunotherapy was also analyzed. Correlation analysis, Cox analysis and LASSO Cox regression were used to construct the CDKL3-related autophagy (CrA) risk score model. The relationship between CDKL3 expression and postoperative pathological complete response (pCR) rate in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) was evaluated using Immunohistochemical staining (IHC). The relationship between CDKL3 expression and autophagy induction was confirmed by immunofluorescence staining and western blot, and the effect of CDKL3 expression on macrophage polarization was verified by flow cytometry.ResultsHigh expression of CDKL3 was found in ESCA and was associated with poor prognosis in ESCA. Moreover, CDKL3 expression was negatively correlated with tumor-infiltrating immune cells (TIICs), the integrality of the cancer immunity cycles, and anti-tumor signatures, while CDKL3 expression was positively correlated with suppressive TME-related chemokines and receptors, immune hyperprogressive genes, and suppressive immune checkpoint, resulting in immunosuppressive TME formation in ESCA. An analysis of immunotherapy cohorts of the ESCA and pan-cancer showed a better response to immunotherapy in tumor patients with lower CDKL3 levels. The CrA risk score model was constructed and validated to accurately predict the prognosis of ESCA. Notably, the CrA risk score of ESCA patients was significantly positively correlated with M2 macrophages. Furthermore, knockdown CDKL3 in KYSE150 cells could inhibit autophagy induction and M2 macrophage polarization. And, radiation could downregulate CDKL3 expression and autophagy induction, while ESCC patients with high CDKL3 expression had a significantly lower response rate after nCRT than those with low CDKL3 expression.ConclusionCDKL3 may play an important role in anti-tumor immunity by regulating autophagy to promote the formation of immunosuppressive TME, thus playing a critical role in the prognosis of ESCA.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

Bi,

Liu,

Qin

et al. 2024

Front. Immunol.

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“…Across PC xenograft and mice models, autophagy inhibition via small hairpin RNA (shRNA) or small molecule inhibitors targeting ATG5 causes tumor regression and longer survival because ATG5 and ATG7 proteins are required for autophagosome formation [ 8 , 52 ], and ATG5 or ATG7 gene deletions reduce autophagy effects [ 53 ]. A mouse model with carcinogenic KRAS expression in pancreatic cells in the presence of two, one, or no Atg5 gene copies found that reduced Atg5 protein levels enhance tumor formation, but the absence of Atg5 prevents tumorigenesis [ 54 ]. Therefore, when primary PC cell lines lacking Atg5 were injected into a mouse, they observed improved intrusive and metastatic capability.…”

Section: Interactions For Both Autophagy and Pdacmentioning

confidence: 99%

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

et al. 2022

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Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

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CDKL3 Promotes Non-small Cell Lung Cancer by Suppressing Autophagy Via Activation of PI3K/Akt/mTOR Pathway

Chai

Lei

et al. 2023

Mol Biotechnol

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CDKL3 Targets ATG5 to Promote Carcinogenesis of Esophageal Squamous Cell Carcinoma

Cited by 8 publications

References 27 publications

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

CDKL3 Promotes Non-small Cell Lung Cancer by Suppressing Autophagy Via Activation of PI3K/Akt/mTOR Pathway

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