HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐<i>β</i> and TNFSF13B/VEGF‐A Axis

Yin, Lei; Li, Wenjia; Chen, Xuxiao; Wang, Ronghao; Zhang, Tao; Meng, Jialin; Zhao, Li; Li, Xu; Yin, Rui; Cheng, Bo; Yang, Huan

doi:10.1002/advs.202206955

Cited by 12 publications

(3 citation statements)

References 48 publications

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“…Meanwhile, an elevated activation of TGF-β pathway was also observed, corroborating prior evidence for a beneficial role of TGF-β in ccRCC (Fig. 4 A) [ 38 ]. In our previous findings, we have identified and validated dichotomous ccRCC immune subtypes with prognosis and TKI responses [ 39 ].…”

Section: Resultssupporting

confidence: 87%

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma

Xu,

Jiang,

Liu

et al. 2024

Cancer Immunol Immunother

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Background Homologous recombination deficiency (HRD), though largely uncharacterized in clear cell renal cell carcinoma (ccRCC), was found associated with RAD51 loss of expression. PBRM1 is the second most common mutated genes in ccRCC. Here, we introduce a HRD function-based PBRM1-RAD51 ccRCC classification endowed with diverse immune checkpoint blockade (ICB) responses. Methods Totally 1542 patients from four independent cohorts were enrolled, including our localized Zhongshan hospital (ZSHS) cohort and Zhongshan hospital metastatic RCC (ZSHS-mRCC) cohort, The Cancer Genome Atlas (TCGA) cohort and CheckMate cohort. The genomic profile and immune microenvironment were depicted by genomic, transcriptome data and immunohistochemistry. Results We observed that PBRM1-loss ccRCC harbored enriched HRD-associated mutational signature 3 and loss of RAD51. Dual-loss of PBRM1 and RAD51 identified patients hyper-sensitive to immunotherapy. This dual-loss subtype was featured by M1 macrophage infiltration. Dual-loss was, albeit homologous recombination defective, with high chromosomal stability. Conclusions PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.

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Section: Resultssupporting

confidence: 87%

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma

Xu,

Jiang,

Liu

et al. 2024

Cancer Immunol Immunother

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“…Abnormally high levels of VEGF-A primarily control angiogenesis, which is the development of new blood vessels from already existing ones. This spike in VEGF-A is frequently triggered by tumor hypoxia during lesion expansion, but it can also arise from defects in the primary HIF pathway ( 22 ). Additionally, disruptions that occur during other stages of vascular development, i.e., PDGF-BB and Notch, contribute to and hasten the vascularization of tumors ( 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma

Lan,

Feng,

et al. 2024

Front. Oncol.

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ObjectivesMedical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years.MethodsFrom the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included.ResultsA cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM’s works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms “hereditary leiomyomatosis” and “fumarate hydratase.”ConclusionThis is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.

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“…In lung cancer cells, it was observed that while SHP2 positively regulates TEM, HOOK1 has the opposite effect [ 24 ]. Nonetheless, other studies have linked HOOK1 to the progression of different types of tumors independently to its proposed interaction with SHP2 [ 20 , 25 , 26 ]. Hence, the precise role of HOOK1 in cancer and its underlying mechanism remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy

Suárez-Martínez,

Piersma,

Pham

et al. 2024

J Exp Clin Cancer Res

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Background Ovarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem cells (CSCs), interactions with the microenvironment, and intratumoral heterogeneity. Therefore, the search for new therapeutic targets, particularly those targeting CSCs, is important for improving patient prognosis. HOOK1 has been found to be transcriptionally altered in a substantial percentage of ovarian tumors, but its role in tumor initiation and development is still not fully understood. Methods The downregulation of HOOK1 was performed in ovarian cancer cell lines using CRISPR/Cas9 technology, followed by growth in vitro and in vivo assays. Subsequently, migration (Boyden chamber), cell death (Western-Blot and flow cytometry) and stemness properties (clonal heterogeneity analysis, tumorspheres assay and flow cytometry) of the downregulated cell lines were analysed. To gain insights into the specific mechanisms of action of HOOK1 in ovarian cancer, a proteomic analysis was performed, followed by Western-blot and cytotoxicity assays to confirm the results found within the mass spectrometry. Immunofluorescence staining, Western-blotting and flow cytometry were also employed to finish uncovering the role of HOOK1 in ovarian cancer. Results In this study, we observed that reducing the levels of HOOK1 in ovarian cancer cells reduced in vitro growth and migration and prevented tumor formation in vivo. Furthermore, HOOK1 reduction led to a decrease in stem-like capabilities in these cells, which, however, did not seem related to the expression of genes traditionally associated with this phenotype. A proteome study, along with other analysis, showed that the downregulation of HOOK1 also induced an increase in endoplasmic reticulum stress levels in these cells. Finally, the decrease in stem-like properties observed in cells with downregulated HOOK1 could be explained by an increase in cell death in the CSC population within the culture due to endoplasmic reticulum stress by the unfolded protein response. Conclusion HOOK1 contributes to maintaining the tumorigenic and stemness properties of ovarian cancer cells by preserving protein homeostasis and could be considered an alternative therapeutic target, especially in combination with inducers of endoplasmic reticulum or proteotoxic stress such as proteasome inhibitors.

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HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis

Cited by 12 publications

References 48 publications

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma

Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy

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