ITGB1BP1, a Novel Transcriptional Target of CD44-Downstream Signaling Promoting Cancer Cell Invasion

Abstract

Breast cancer (BC) is the most common malignancy worldwide and has a poor prognosis, because it begins in the breast and disseminates to lymph nodes and distant organs. While invading, BC cells acquire aggressive characteristics from the tumor microenvironment through several mechanisms. Thus, understanding the mechanisms underlying the process of BC cell invasion can pave the way towards the development of targeted therapeutics focused on metastasis. We have previously reported that the activation of CD44 receptor with its major ligand hyaluronan (HA) promotes BC metastasis to the liver in vivo. Next, a gene expression profiling microarray analysis was conducted to identify and validate CD44-downstream transcriptional targets mediating its pro-metastatic function from RNA samples collected from Tet CD44-induced versus control MCF7-B5 cells. We have already validated a number of novel CD44-target genes and published their underlying signaling pathways in promoting BC cell invasion. From the same microarray analysis, Integrin subunit beta 1 binding protein 1 (ITGB1BP1) was also identified as a potential CD44-target gene that was upregulated (2-fold) upon HA activation of CD44. This report will review the lines of evidence collected from the literature to support our hypothesis, and further discuss the possible mechanisms linking HA activation of CD44 to its novel potential transcriptional target ITGB1BP1.

Keywords:

• ITGB1BP1
• Breast cancer
• CD44
• Hyaluronan
• metastasis

Abbreviations

AKT, Protein kinase B; BC, Breast cancer; CAM, Cell adhesion molecule; CaMKII, Calcium/calmodulin-dependent protein kinase II; Cas, CRISPR-associated proteins; CD44, Cluster of differentiation 44; Cdc42, Cell division control protein 42 homolog; ECM, Extracellular matrix; EMT, Epithelial-mesenchymal transition; ERK, Extracellular-signal-regulated kinase; FAs, Focal adhesions; FAK, Focal adhesion kinase; HA, Hyaluronic acid; ICAP-1, Integrin cytoplasmic-associated protein 1; ITG-β1, Integrin subunit beta-1; ITGB1BP1, Integrin Subunit Beta 1 Binding Protein 1; KRIT-1, Krev interaction trapped protein 1; NLS, Nuclear localization signal; Nm23-H2, Nucleoside diphosphate kinase B; PI3K, phosphoinositide 3-kinase; PAK, p21-activated kinases; PK, Protein kinase; PTB, Phosphotyrosine‐binding domain; Rac1, Ras-related C3 botulinum toxin substrate 1; Rho, Ras homologous; ROCK, Rho-associated protein kinase; Smurf1, Smad, ubiquitin regulatory factor 1; Tet, Tetracycline; TGF-β2, Transforming growth factor beta 2.

Consent for Publication

Yes.

Acknowledgments

We are grateful to Dr Ishita Gupta for minor contribution to this manuscript.

Disclosure

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript, or in the decision to publish the results.

Additional information

Funding

This research was funded by Qatar University (Internal grant number (QUST-1-CAS2019-22)), and the Qatar National Research Foundation: UREP24-117-1-027 and UREP29-186-3-059. Dr Hanan Nazar was awarded a PhD scholarship from the Kuwaiti Government.