PXD054307

PXD054307 is an original dataset announced via ProteomeXchange.

Title	Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells.
Description	Background: Non-Small Cell Lung Cancer (NSCLC) presents as a highly metastatic disease with Kras and P53 as prevalent oncogenic driver mutations. Endocytosis, through its role in receptor recycling and enrichment, is important for cancer cell proliferation and metastasis. Huntingtin Interacting Protein 1 (HIP1) is a clathrin mediated endocytic adapter protein found overexpressed in different cancers. However, conflicting roles both as a tumour promoter and suppressor are reported. HIP1 expression is found repressed at advanced stages and some HIP1-ALK fusions are reported in NSCLC patients. However, the molecular mechanisms and implications of HIP1 depletion are not completely understood. Methods: HIP1 depletion was performed using siRNA transient transfection and validated using immunoblotting for each experiment. HIP1 depleted A549 cells were analysed for deregulated global proteome using label-free LC-MS. Gene expression dataset was analysed using TCGA, GTeX and GEO to explore HIP1 expression in Lung cancer patients. Kaplan–Meier Plotter database was used to analyse the survival correlation between HIP1 mRNA expression in lung cancer patients. Various functional assays such as matrigel based invasion, trans-well migration, soft agar colony, tube formation are performed after HIP1 depletion. NRF2 inhibitor was used after HIP1 knockdown to assess its effect on invasion and soft agar colony formation. Results: In silico analysis of HIP1 transcript expression reveals that it is reduced in high-grade and metastatic lung cancer patients correlating with poor survival. Global proteome profiling reveals that HIP1 depleted A549 cells are enriched in pathways associated with metabolism, proliferation and survival. Molecular and functional analysis indicate higher invasive ability of HIP1 depleted cells. The secretome from HIP1 depleted cells also increases the angiogenic potential of HUVEC cells. NRF2 inhibition in HIP1 depleted cells reduces invasion of NSCLC cells with different driver mutations.  Conclusion: Our study shows that HIP1 depletion leads to activation of various molecular pathways responsible for cell proliferation and survival. Additionally, enhancement of invasion in HIP1 depleted subsets of NSCLC cells is via upregulation of NRF2 and can be reversed by its inhibitor.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_02:40:13.366.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shivani Arora Mittal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-28 11:16:14	ID requested
⏵ 1	2024-10-17 02:40:14	announced

Prasad P, Chongtham J, Tripathi SC, Ganguly NK, Mittal SA, Srivastava T, Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells. Biochem Biophys Res Commun, 733():150676(2024) [pubmed]

10.1016/j.bbrc.2024.150676;

submitter keyword: NSCLC, HIP1, NRF2

Dr Shivani mittal
contact affiliation	Associate Professor, Department of biotechnology and research, Sir Ganga ram hospital, New Delhi -110060, Delhi, India
contact email	shivani.mittal@sgrh.com
lab head
Shivani Arora Mittal
contact affiliation	Department of Biotechnology & Research, Sir Ganga Ram Hospital
contact email	shivani.mittal@sgrh.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054307
     1. Label: PRIDE project
     2. Name: Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells.