TY - JOUR
T1 - Mechanistic role of HPV-associated early proteins in cervical cancer
T2 - Molecular pathways and targeted therapeutic strategies
AU - Bhattacharjee, Rahul
AU - Das, Sabya Sachi
AU - Biswal, Smruti Sudha
AU - Nath, Arijit
AU - Das, Debangshi
AU - Basu, Asmita
AU - Malik, Sumira
AU - Kumar, Lamha
AU - Kar, Sulagna
AU - Singh, Sandeep Kumar
AU - Upadhye, Vijay Jagdish
AU - Iqbal, Danish
AU - Almojam, Suliman
AU - Roychoudhury, Shubhadeep
AU - Ojha, Shreesh
AU - Ruokolainen, Janne
AU - Jha, Niraj Kumar
AU - Kesari, Kavindra Kumar
N1 - Funding Information:
Dr. Niraj Kumar Jha is thankful to Sharda University for the infrastructure and facility. The author would like to thank Deanship of Scientific Research at Majmaah University for supporting this work under project number No. R-2022-68 . Kavindra Kumar Kesari and Janne Ruokolainen thanking Aalto University for providing open access support. The authors would like to acknowledge the support from their respective institutes throughout the review writing process.
PY - 2022/6
Y1 - 2022/6
N2 - Purpose: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. Methods: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. Results: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. Conclusion: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.
AB - Purpose: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. Methods: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. Results: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. Conclusion: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.
KW - Cervical cancer
KW - E proteins
KW - HPV
KW - Molecular mechanisms
KW - Signaling pathways
KW - Therapeutic targets
UR - http://www.scopus.com/inward/record.url?scp=85129648484&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2022.103675
DO - 10.1016/j.critrevonc.2022.103675
M3 - Review Article
C2 - 35381343
AN - SCOPUS:85129648484
SN - 1040-8428
VL - 174
SP - 1
EP - 17
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
M1 - 103675
ER -