Dataset Information

Cyclin Dependent Kinase 4 (CDK4) maintains cell cytoskeleton integrity and behavior in Triple Negative Breast Cancer (TNBC) cells

ABSTRACT: Cyclin-Dependent Kinase 4 (CDK4) is best known for its role in cell cycle progression, but its contribution to cellular architecture is less understood. Here, we identify CDK4 as a regulator of cytoskeletal homeostasis in triple-negative breast cancer (TNBC). CDK4 phosphorylates the RhoGAP Myo9b at serine 1935, enhancing its activity and suppressing RhoA–ROCK–mediated actomyosin contractility. Loss or inhibition of CDK4 disrupts cell morphology, destabilizes the actin cytoskeleton, and increases contractility, alongside collapse of the intermediate filament network, including vimentin disorganization and altered mitochondrial distribution. CDK4-deficient cells also show faster but less directed migration. In vivo, tumors derived from CDK4WT and CDK4KO MDA-MB-231 cells implanted in the mammary fat pad display elevated pMLC levels by IHC, consistent with increased contractility, while proteomic analysis reveals enrichment of cytoskeletal pathways. Transcriptomic analyses (SCAN-B, TCGA, I-SPY2) further show that low CDK4 activity correlates with enhanced EMT, migration, metastasis, and RhoA signaling programs in TNBC. Together, these findings establish CDK4 as an upstream regulator of cytoskeletal integrity, linking actin dynamics, intermediate filament organization, and cell behavior, and reveal a structural role beyond its canonical function in cell cycle control.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Lluis Fajas

LAB HEAD: Lluis Fajas Coll

PROVIDER: PXD079448 | Pride | 2026-06-22

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	260522_Parashar_21572_130min_2ul.raw	Raw
	260522_Parashar_21573_130min_2ul.raw	Raw
	260522_Parashar_21574_130min_2ul.raw	Raw
	260522_Parashar_21575_130min_2ul.raw	Raw
	260522_Parashar_21576_130min_2ul.raw	Raw

Items per page:

1 - 5 of 15

Similar Datasets

Project description:We have developed cdk4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) to study lung cancer pathogenesis. By studying the oncogenic effect of common lung cancer alterations (p53, KRAS, and c-MYC) we demonstrate the ability of this model to characterize the stepwise transformation of bronchial epithelial cells to full malignancy. Using HBECs derived from multiple individuals we found: 1) the combination of five genetic alterations (p53, KRASV12, c-MYC, CDK4 and hTERT) is sufficient for full tumorigenic conversion of HBECs; 2) high levels of KRASV12 are required for full malignant transformation of HBECs, however these levels also stimulate oncogene-induced senescence; 3) RAS-induced senescence is largely bypassed with loss of p53 function; 4) over-expression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; 5) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; 6) serum-induced epithelial-to-mesenchymal transition (EMT) increases in vivo tumorigenicity; 7) genetically-identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation as well as sensitivity to standard platinum-based chemotherapies; and 8) an mRNA signature derived from tumorigenic and non-tumorigenic clones is predictive of outcome in lung cancer patients. Collectively, we demonstrate this HBEC model system can be used to study the effect of oncogenic mutations on malignant progression, oncogene-induced senescence, and EMT along with clinically translatable applications such as development of prognostic signatures and drug response phenotypes. Human bronchial epithelial cells (HBECs) immortalized with cdk4 and hTERT were transformed with p53 knockdown, KrasV12 and cMYC over-expression and profiled on Illumina HumanHT-12 V4.0 expression beadchips. Transformed HBECs were grown in two different growth media: KSFM (defined, serum-free medium) or R10 (RPMI with 10% FBS) as indicated. Clones were isolated from HBECs with sh-p53 + KrasV12 and sh-p53 + KrasV12 + cMYC.

Dataset Information

Cyclin Dependent Kinase 4 (CDK4) maintains cell cytoskeleton integrity and behavior in Triple Negative Breast Cancer (TNBC) cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets