ArticleOncogene2015
Hematopoietic PBX-interacting protein (HPIP) is over expressed in breast infiltrative ductal carcinoma and regulates cell adhesion and migration through modulation of focal adhesion dynamics.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairmentActa pharmaceutica Sinica. B · 2025Article
- HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.Science advances · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- CDC20: a novel therapeutic target in cancer.American journal of translational research · 2023Review
- A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein.Cell death discovery · 2021Article
- Review
- Hematopoietic PBX-interacting protein is a substrate and an inhibitor of the APC/C-Cdc20 complex and regulates mitosis by stabilizing cyclin B1.The Journal of biological chemistry · 2019Article
- Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.Nature communications · 2019Article
- Article
- HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- HPIP: a predictor of lymph node metastasis and poor survival in cervical cancer.OncoTargets and therapy · 2017Article
- Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study.OncoTargets and therapy · 2017Article
- The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway.Oncogenesis · 2016Article
- Identification of hallmarks of lung adenocarcinoma prognosis using whole genome sequencing.Oncotarget · 2015Article
- Hematopoietic pre-B cell leukemia transcription factor interacting protein is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion.Cancer science · 2015Article
- HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The scaffolding protein, hematopoietic PBX-interacting protein (HPIP/PBXIP1), regulates cell migration necessary for cancer cell dissemination. However, the mechanism that governs this process remains unknown. We show here that HPIP expression is associated with stages of breast cancer where cell dissemination results in poor patient outcome. Our investigation finds a novel association of HPIP with focal adhesion kinase (FAK) regulating FA dynamics. Interestingly, this interaction that led to activation of FAK protein was mediated by the C-terminal domain of HPIP and not the typical integrin-binding motif. Further, short hairpin RNA-mediated knockdown of FAK expression significantly reduced HPIP-induced cell migration indicating participation of FAK pathway. Live-cell time-lapse imaging and biochemical analysis further established the role of HPIP in microtubule-induced FA disassembly. We also found that HPIP-mediated MAPK activation led to phosphorylation and subsequent activation of calpain2, and the activated calpain2 in turn proteolyses FA protein, talin. Interestingly, HPIP is also proteolysed by calpain2 in breast cancer cells. The proteolysis of HPIP and talin by calpain2, and the activation of calapin2 by HPIP-mediated MAPK phosphorylation, is a novel regulatory axis to modulate the cell migration signal. Together, we have determined HPIP as a novel activator of FAK and a new substrate of calpain2. These molecular interactions between HPIP and FAK, and HPIP and calpain2 regulate cell adhesion and migration through modulation of FA dynamics.
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