FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4316499843> ?p ?o ?g. }

• W4316499843 abstract "Activated Cdc42-associated kinase 1 (ACK1) is a promising druggable target for cancer, but its inhibitors only showed moderate effects in clinical trials. The study aimed to investigate the underlying mechanisms and improve the antitumor efficacy of ACK1 inhibitors.RNA-seq was performed to determine the downstream pathways of ACK. Using Lasso Cox regression analysis, we built a risk signature with ACK1-related autophagy genes in the lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) project. The performance of the signature in predicting the tumor immune environment and response to immunotherapy and chemotherapy were assessed in LUAD. CCK8, mRFP-GFP-LC3 assay, western blot, colony formation, wound healing, and transwell migration assays were conducted to evaluate the effects of the ACK1 inhibitor on lung cancer cells. A subcutaneous NSCLC xenograft model was used for in vivo study.RNA-seq revealed the regulatory role of ACK1 in autophagy. Furthermore, the risk signature separated LUAD patients into low- and high-risk groups with significantly different prognoses. The two groups displayed different tumor immune environments regarding 28 immune cell subsets. The low-risk groups showed high immune scores, high CTLA4 expression levels, high immunophenoscore, and low DNA mismatch repair capacity, suggesting a better response to immunotherapy. This signature also predicted sensitivity to commonly used chemotherapy and targeted drugs. In vitro, the ACK1 inhibitors (AIM-100 and Dasatinib) appeared to trigger adaptive autophagy-like response to protect lung cancer cells from apoptosis and activated the AMPK/mTOR signaling pathway, partially explaining its moderate antitumor efficacy. However, blocking lysosomal degradation with chloroquine/Bafilamycine A1 or inhibiting AMPK signaling with compound C/shPRKAA1 enhanced the ACK1 inhibitor's cytotoxic effects on lung cancer cells. The efficacy of the combined therapy was also verified using a mouse xenograft model.The resulting signature from ACK1-related autophagy genes robustly predicted survival and drug sensitivity in LUAD. The lysosomal degradation inhibition improved the therapeutic effects of the ACK1 inhibitor, suggesting a potential role for autophagy in therapy evasion." @default.
• W4316499843 created "2023-01-16" @default.
• W4316499843 creator A5005538469 @default.
• W4316499843 creator A5017613131 @default.
• W4316499843 creator A5032050928 @default.
• W4316499843 creator A5034485107 @default.
• W4316499843 creator A5040662878 @default.
• W4316499843 creator A5075168223 @default.
• W4316499843 creator A5082669810 @default.
• W4316499843 creator A5085823894 @default.
• W4316499843 date "2023-01-16" @default.
• W4316499843 modified "2023-10-13" @default.
• W4316499843 title "Improvement of ACK1-targeted therapy efficacy in lung adenocarcinoma using chloroquine or bafilomycin A1" @default.
• W4316499843 cites W1488119624 @default.
• W4316499843 cites W1806194585 @default.
• W4316499843 cites W1913291305 @default.
• W4316499843 cites W1964272901 @default.
• W4316499843 cites W1995117011 @default.
• W4316499843 cites W2001847316 @default.
• W4316499843 cites W2013750047 @default.
• W4316499843 cites W2018663224 @default.
• W4316499843 cites W2042619042 @default.
• W4316499843 cites W2045030989 @default.
• W4316499843 cites W2075294566 @default.
• W4316499843 cites W2081511916 @default.
• W4316499843 cites W2084946596 @default.
• W4316499843 cites W2091415498 @default.
• W4316499843 cites W2098752359 @default.
• W4316499843 cites W2140912399 @default.
• W4316499843 cites W2149055519 @default.
• W4316499843 cites W2150909784 @default.
• W4316499843 cites W2154345947 @default.
• W4316499843 cites W2157699677 @default.
• W4316499843 cites W2166339706 @default.
• W4316499843 cites W2346133077 @default.
• W4316499843 cites W2557869208 @default.
• W4316499843 cites W2615994102 @default.
• W4316499843 cites W2622499649 @default.
• W4316499843 cites W2625470034 @default.
• W4316499843 cites W2740618823 @default.
• W4316499843 cites W2752326209 @default.
• W4316499843 cites W2764117127 @default.
• W4316499843 cites W2765831845 @default.
• W4316499843 cites W2783897381 @default.
• W4316499843 cites W2784371446 @default.
• W4316499843 cites W2784868445 @default.
• W4316499843 cites W2801496022 @default.
• W4316499843 cites W2883706067 @default.
• W4316499843 cites W2884412731 @default.
• W4316499843 cites W2884611203 @default.
• W4316499843 cites W2889646458 @default.
• W4316499843 cites W2900082702 @default.
• W4316499843 cites W2944675676 @default.
• W4316499843 cites W2949273159 @default.
• W4316499843 cites W2974416662 @default.
• W4316499843 cites W2992033410 @default.
• W4316499843 cites W3005827630 @default.
• W4316499843 cites W3012033976 @default.
• W4316499843 cites W3024740892 @default.
• W4316499843 cites W3033093656 @default.
• W4316499843 cites W3044334802 @default.
• W4316499843 cites W3090007237 @default.
• W4316499843 cites W3106689543 @default.
• W4316499843 cites W3106933574 @default.
• W4316499843 cites W3108936441 @default.
• W4316499843 cites W3109271117 @default.
• W4316499843 cites W3109856011 @default.
• W4316499843 cites W3121213825 @default.
• W4316499843 cites W3136819448 @default.
• W4316499843 cites W3164679520 @default.
• W4316499843 cites W3186632095 @default.
• W4316499843 cites W3197593329 @default.
• W4316499843 cites W3206956285 @default.
• W4316499843 cites W3209094303 @default.
• W4316499843 cites W3210335623 @default.
• W4316499843 cites W3211154461 @default.
• W4316499843 cites W4220724162 @default.
• W4316499843 cites W4221032018 @default.
• W4316499843 cites W4226159165 @default.
• W4316499843 doi "https://doi.org/10.1186/s10020-023-00602-z" @default.
• W4316499843 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36647009" @default.
• W4316499843 hasPublicationYear "2023" @default.
• W4316499843 type Work @default.
• W4316499843 citedByCount "0" @default.
• W4316499843 crossrefType "journal-article" @default.
• W4316499843 hasAuthorship W4316499843A5005538469 @default.
• W4316499843 hasAuthorship W4316499843A5017613131 @default.
• W4316499843 hasAuthorship W4316499843A5032050928 @default.
• W4316499843 hasAuthorship W4316499843A5034485107 @default.
• W4316499843 hasAuthorship W4316499843A5040662878 @default.
• W4316499843 hasAuthorship W4316499843A5075168223 @default.
• W4316499843 hasAuthorship W4316499843A5082669810 @default.
• W4316499843 hasAuthorship W4316499843A5085823894 @default.
• W4316499843 hasBestOaLocation W43164998431 @default.
• W4316499843 hasConcept C104317684 @default.
• W4316499843 hasConcept C143998085 @default.
• W4316499843 hasConcept C150194340 @default.
• W4316499843 hasConcept C190283241 @default.
• W4316499843 hasConcept C203014093 @default.
• W4316499843 hasConcept C203522944 @default.

• next