Targeting the secretory program of 3q-amplified lung cancers DOI Creative Commons
Luis A. Pardo, Jim C. Norman

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(12)

Published: June 16, 2024

Designing strategies to target cell proliferation has been a priority of cancer researchers for decades. However, targeting the secretory programs transformed cells can influence other features such as survival, migration, and communication with tumor stroma. In this issue JCI, Tan colleagues describe functional cooperativity between Golgi-resident proteins Golgi integral membrane protein 4 (GOLIM4) ATPase pathway Ca2+ transporting 1 (ATP2C1) in coordination program 3q-amplified cancers. Targeting these tumors manganese (Mn2+) promoted GOLIM4 degradation imposed blockade that impaired progression stromal recruitment mice. These findings highlight therapeutic malignancies provide promising strategy treat progression.

Language: Английский

Chromosomal 3q amplicon encodes essential regulators of secretory vesicles that drive secretory addiction in cancer DOI Creative Commons
Xiaochao Tan,

Shike Wang,

Guan-Yu Xiao

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(12)

Published: April 25, 2024

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon serves as platform for regulation in cancer. The encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show GOLIM4 recruits ATP2C1 phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading bending vesicle scission. depletion disrupts complex, resulting blockade inhibits progression of 3q-amplified malignancies. In addition its role scaffold, maintains intracellular manganese (Mn) homeostasis by binding excess Mn lumen, which initiates routing Mn-bound lysosomes degradation. treatment types malignancies degrading GOLIM4, interrupts pro-survival autocrine loops attenuates pro-metastatic processes microenvironment. Potentially underlying selective activity against malignancies, co-amplification increases influx into more rapid degradation GOLIM4. These findings functional cooperativity between co-amplified genes underlies secretion targetable addiction

Language: Английский

Citations

4
Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer DOI Creative Commons

Linlin Lou,

Keren Peng,

Shumin Ouyang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 7, 2025

Abstract Background Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying interaction between SCLC and microenvironment, fostering metastasis, remain unclear. Methods patient tissue array, bioinformatics analysis were performed to demonstrate role periostin (POSTN) progression, prognosis. Cell migration, invasion sphere formation assay determine oncogenic POSTN. RNA sequencing was utilized identify key signaling pathway regulated by Immunoprecipitation, immunofluorescence co-culture system used clarify mechanism POSTN-NOTCH1 axis tumor cells-hepatic stellate cells (HSCs) crosstalk. Subcutaneous xenograft model metastasis established examine anti-tumor growth metastases effect targeting axis. Results Elevated expression POSTN correlated accelerated progression Conditioned medium rich derived from tumors demonstrates ability activate HSCs microenvironment. Mechanistically, emerges as binding partner membrane receptor NOTCH1 transducing extracellular signals intracellular fibroblasts. Furthermore, proves effective suppressing inhibiting This study elucidates that SCLC-derived secreted protein interacts on promote activation HSCs, thereby providing favorable microenvironment Conclusion These findings uncover intricate communications mediated context Consequently, promising therapeutic strategy metastatic SCLC.

Language: Английский

Citations

0
Downregulation of AATK enhances susceptibility to ferroptosis by promoting endosome recycling in gefitinib‐resistant lung cancer cells DOI Open Access

Wei‐Chang Lee,

Sin‐Hua Moi, Sheau‐Fang Yang

et al.

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Ferroptosis has been characterised by disruption of the cell membrane through iron‐related lipid peroxidation. However, regulation iron homeostasis in lung cancer cells that are resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) remains unclear. Transcriptome analysis identified a significant downregulation apoptosis‐associated ( AATK ) mRNA expression gefitinib‐resistant PC9 (PC9‐GR) cells, which were found be more susceptible ferroptosis inducers. An in‐depth publicly available datasets revealed was associated with lymph node metastasis and poor prognosis patients adenocarcinoma. Knockdown AATK‐sensitised PC9, HCC827, H441 inducer RSL3, whereas ectopic reduced RSL3‐induced death PC9‐GR HCC827‐GR cells. Compared exhibited higher transferrin uptake, endosome recycling rate, increased intracellular levels. Blocking transport Mechanistic studies showed localised both early endosomes. facilitated elevated ferrous (Fe 2+ levels Conversely, delayed Fe Inhibition downregulation‐induced accumulation decreased ferroptosis. Taken together, our study indicates contributes accumulation, leading an susceptibility EGFR‐TKI‐resistant © 2025 The Pathological Society Great Britain Ireland.

Language: Английский

Citations

0
Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention DOI Creative Commons

Lin Tang,

Peng Shen, Xiaoying Zhuang

et al.

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 17, 2025

ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.

Language: Английский

Citations

0
Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities DOI
Tamás Balla

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2025, Volume and Issue: unknown, P. 159615 - 159615

Published: April 1, 2025

Language: Английский

Citations

0
Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities DOI
Alicia Llorente Lope, Gurpreet K. Arora, Rabi Murad

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

Citations

0
Dichotomous roles of ACBD3 in NSCLC growth and metastasis DOI Creative Commons
Xiaochao Tan, Chao‐Liang Wu, Priyam Banerjee

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: April 6, 2025

Abstract Lung cancer continues to be the leading cause of cancer-related deaths globally. Unraveling regulators behind lung growth and its metastatic spread, along with understanding underlying mechanisms, is crucial for developing novel effective therapeutic strategies. While much research has focused on identifying potential oncogenes or tumor suppressors, roles certain genes can vary depending context may even exhibit contradictory effects. In this study, we demonstrate that acyl-CoA binding domain containing 3 (ACBD3), a Golgi resident protein, promotes primary by recruiting phosphatidylinositol (PI)-4-kinase IIIβ (PI4KB) Golgi, thereby enhancing oncogenic secretion in chromosome 1q-amplified cells. Conversely, 1q-diploid cells, ACBD3 acts as suppressor metastasis inhibiting NOTCH signaling pathway reducing cell motility. This highlights intricacy progression cautions against simplistic approaches targeting individual therapy.

Language: Английский

Citations

0
PI4K2A: a novel potential therapeutic target for lung cancer DOI Open Access
Camila Machado Baldavira, Tabatha Gutierrez Prieto, María Aparecida Nagai

et al.

Translational Lung Cancer Research, Journal Year: 2024, Volume and Issue: 13(1), P. 199 - 204

Published: Jan. 1, 2024

Language: Английский

Citations

1
An advanced comprehensive muti-cell-type-specific model for predicting anti-PD-1 therapeutic effect in melanoma DOI Creative Commons

Wei Sun,

Yu Zhu,

Zijian Zou

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 2127 - 2150

Published: Jan. 1, 2024

Immune checkpoint inhibitors targeting the programmed cell death (PD)-1/PD-L1 pathway have promise in patients with advanced melanoma. However, drug resistance usually results limited patient benefits. Recent single-cell RNA sequencing studies elucidated that MM display distinctive transcriptional features of tumor cells, immune cells and interstitial including loss antigen presentation function exhaustion CD8+T extracellular matrix secreted by fibroblasts to prevents infiltration, which leads a poor response (ICIs). subgroups beneficial anti-tumor immunity model developed them remain be further identified.

Language: Английский

Citations

1
Analysis of the mRNA export protein ZC3H11A in HCMV infection and pan-cancer DOI Creative Commons
Jiawen Li, Minho Song, Zhen Liu

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 15, 2023

Background We have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which has been recently by our research group in regulating mRNA export under stress conditions. And also, thorough analysis ZC3 pan-cancer and omics data are yet to be conducted. Methods The transcriptomes glioma cells were assessed RNA sequencing. level following validated measured qRT-PCR Western-blot. expression information across analyzed visualized R packages. localization was IHC images from HPA. proteomics transcriptomics different cancers extracted CPTAC portal, comparisons conducted with Python script. genetic alteration, survival prognosis, immune infiltration cBioPortal, TCGA, TIMER2 databases. interaction networks revealed STRING, GEPIA2 TCGA. Results Genes processing pathways upregulated validated. also status generally at high levels cancers, although varied among cancer types. tumor localized whereas normal it mainly found cytoplasmic/membranous. However, some types, increase not accompanied significant elevation level. Additionally, indicated elevated primarily linked negative prognosis majority but still depending on Our annotation suggested ZC3-related proteins involved clusters. Conclusion demonstrated significantly impacted gliomas. Furthermore, identified set genes exhibiting analogous patterns TCGA cohorts, implying potential functional role for processing. study provided valuable insights into new progression. These results lay foundation next regulatory mechanism virus-infected tumors.

Language: Английский

Citations

3