Proteomics strategies to analyze HPV-transformed cells: relevance to cervical cancer

Abstract

Cervical cancer is the second most common malignant tumor among women worldwide. The initiating event of cervical cancer is the infection with certain types of human papillomavirus (HPV). Interestingly, viral oncogene expression is necessary but not per se sufficient to promote cervical cancer and other factors are involved in neoplastic progression. Thus, major research efforts should be focused to identify novel co-carcinogenic factors and to understand the mechanisms played into tumor development. To reach this goal, proteomics strategies are powerful tools and a number of studies performed by following this approach have contributed to unravel the interplay between viral infection and protein dysfunction that ultimately results in cancer. The present review summarizes the most relevant findings obtained by applying proteomics technologies to both cell culture models and human tissue specimens. The results suggest that viral oncogenes selectively interact with a subset of intracellular proteins mainly involved in apoptosis resistance, cell growth and differentiation and cell transformation.

Keywords::

• 2D electrophoresis
• cell transformation
• cervical cancer
• E6 and E7 oncogenes
• HPV
• MALDI-TOF
• proteomics

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The infection with human papillomavirus is the primary and causative event in the development of cervical cancer.

• • HPV infection, although necessary, is not per se sufficient to induce cervical cancer.

• • E6, E7 and E5 are the oncogenic proteins involved in cell transformation and cancer promotion.

• • The progression of infected cells to the full neoplastic phenotype is fostered by a number of known and unknown factors.

• • Proteomics strategies involved complementary tools for the characterization of host-cell interactions that are essential to understand the pro-carcinogenic modulation of key cellular messengers.

• • Ongoing analysis of selected proteins showing differential expression between infected cells compared to controls, will contribute to prove their potential applicability to squamous cervical cancer-specific diagnosis and therapeutic applications by quantitative approaches (liquid chromatography mass spectrometry, isobaric tag for relative and absolute quantitation, etc).

• • Regulation of protein function results from a number of post-translational modifications (PTM) which are critical for its function, as they can affect activity, stability, localization and turnover.

• • Targeted proteomics approaches will probably contribute to unravel the complexity of PTM modifications orchestrated by HPV oncogenes to identify novel key factors.

Notes