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Osteopontin -- a promising biomarker for cancer therapy.

ABSTRACT: Osteopontin (OPN), a multifunctional protein, has emerged as a potentially valuable biomarker for diagnosing and treating cancers. Recent research focuses on its involvement in tumor biology including the cell proliferation, survival, angiogenesis, invasion, and metastasis. Understanding the molecular mechanisms and pharmacological effects of OPN in cancer development could lead to new targets for improving cancer diagnosis and treatment. This review explains how the structurally conserved domains of OPN are associated with OPN signaling mediators and CD44, and how the conserved OPN domains determine biological functions. The authors have reviewed representative works of OPN expression in breast cancer and colorectal cancer to elucidate the relationship between OPN and cancer/tumor biology. It has also been shown that the prognostic sensitivity in non-small cell lung cancer, hepatocellular carcinoma, gastric cancer, and ovarian cancer improved compared to the individual marker when OPN was analyzed in conjunction with other markers. The therapeutic approaches based on OPN inhibitors are discussed to illustrate recent research progress. Previous clinical data has indicated that OPN has played a unique role in cancer development, but further investigation is required to understand the underlying mechanism. More clinical trials are also required to examine the applicability and efficacy of OPN inhibitors in cancer therapy.

SUBMITTER: Wei R

PROVIDER: S-EPMC5560134 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Osteopontin -- a promising biomarker for cancer therapy.

Wei Ran R Wong Janet Pik Ching JPC Kwok Hang Fai HF

Journal of Cancer 20170715 12

Osteopontin (OPN), a multifunctional protein, has emerged as a potentially valuable biomarker for diagnosing and treating cancers. Recent research focuses on its involvement in tumor biology including the cell proliferation, survival, angiogenesis, invasion, and metastasis. Understanding the molecular mechanisms and pharmacological effects of OPN in cancer development could lead to new targets for improving cancer diagnosis and treatment. This review explains how the structurally conserved domai ...[more]

PMID: 28819419

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Project description:BackgroundOsteopontin (Eta, secreted sialoprotein 1, opn) is secreted from different cell types including cancer cells. Three splice variant forms namely osteopontin-a, osteopontin-b and osteopontin-c have been identified. The main astonishing feature is that osteopontin-c is found to be elevated in almost all types of cancer cells. This was the vital point to consider it for sequence analysis and structure predictions which provide ample chances for prognostic, therapeutic and preventive cancer research.MethodsOsteopontin-c gene sequence was determined from Breast Cancer sample and was translated to protein sequence. It was then analyzed using various software and web tools for binding pockets, docking and druggability analysis. Due to the lack of homological templates, tertiary structure was predicted using ab-initio method server - I-TASSER and was evaluated after refinement using web tools. Refined structure was compared with known bone sialoprotein electron microscopic structure and docked with CD44 for binding analysis and binding pockets were identified for drug designing.ResultsSignal sequence of about sixteen amino acid residues was identified using signal sequence prediction servers. Due to the absence of known structures of similar proteins, three dimensional structure of osteopontin-c was predicted using I-TASSER server. The predicted structure was refined with the help of SUMMA server and was validated using SAVES server. Molecular dynamic analysis was carried out using GROMACS software. The final model was built and was used for docking with CD44. Druggable pockets were identified using pocket energies.ConclusionsThe tertiary structure of osteopontin-c was predicted successfully using the ab-initio method and the predictions showed that osteopontin-c is of fibrous nature comparable to firbronectin. Docking studies showed the significant similarities of QSAET motif in the interaction of CD44 and osteopontins between the normal and splice variant forms of osteopontins and binding pockets analyses revealed several pockets which paved the way to the identification of a druggable pocket.

Dataset Information

Osteopontin -- a promising biomarker for cancer therapy.

Publications

Osteopontin -- a promising biomarker for cancer therapy.

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