JAK2 V617F mutation, multiple hematologic and non-hematologic processes: an association?

Liu, Kenneth G.; Verma, Amit; Derman, Olga; Kornblum, Noah; Janakiram, Murali; Braunschweig, Ira; Battini, Ramakrishna

doi:10.1186/s40364-016-0073-4

Cited by 2 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, the levels of JAK2 autophosphorylation and activation are increased in many cancers, particularly those of a haematopoietic origin. Several of these cancers harbour the JAK2 V617F mutant, which drives cell proliferation and can enable immune escape [50][51][52]. Inhibition of JAK2 using the non-selective compound AG490 has demonstrated that JAK2 activity is required for STAT3 phosphorylation and viral oncogene expression in HPV+ cervical cancer cells [47].…”

Section: Discussionmentioning

confidence: 99%

JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death

Morgan

Macdonald

2019

Cancers

View full text Add to dashboard Cite

Persistent infection with high-risk human papillomavirus (HPV) is the underlying cause of ~5% of all human cancers, including the majority of cervical carcinomas and many other ano-genital and oral cancers. A major challenge remains to identify key host targets of HPV and to reveal how they contribute to virus-mediated malignancy. The HPV E6 oncoprotein aberrantly activates the signal transducer and activator of transcription 3 (STAT3) transcription factor and this is achieved by a virus-driven increase in the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in HPV positive cervical cancers cells. Crucially, STAT3 activity is essential for the proliferation and survival of cervical cancer cells, suggesting that targeting STAT3 may have therapeutic potential. Unfortunately, the development of direct STAT3 inhibitors has been problematic in the clinic due to toxicity issues identified in early stage trials. To overcome this issue, we focused on the protein Janus kinase 2 (JAK2), which phosphorylates STAT3 and is essential for STAT3 activation. Here, we demonstrate that inhibiting JAK2 reduces cell proliferation and induces apoptosis in HPV transformed cervical cancer cells. We further establish that this is due to inhibition of phosphorylation of the JAK2 substrates STAT3 and STAT5. Finally, we demonstrate that the clinically available JAK2 inhibitor Ruxolitinib synergises with cisplatin in inducing apoptosis, highlighting JAK2 as a promising therapeutic target in HPV-driven cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death

Morgan

Macdonald

2019

Cancers

View full text Add to dashboard Cite

show abstract

“…10 There is only a rare case depicting the association of JAK2 V617F mutation with myeloproliferative, lymphoproliferative, and solid neoplasms. 24 Here, for the first time, we provide evidence that upregulation of JAK2 is associated with lung adenocarcinoma LN metastasis. Furthermore, downregulation of JAK2 was found to significantly suppress the proliferation, migration, and invasion of lung adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 61%

“…10 There is only a rare case depicting the association of JAK2 V617F mutation with myeloproliferative, lymphoproliferative, and solid neoplasms. 24…”

Section: Discussionmentioning

confidence: 99%

JAK2 variations and functions in lung adenocarcinoma

Jin

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers. Recently our study found that JAK2 might play an important role in lung cancer pathogenesis. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the variations and functions of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). The shRNA and overexpression plasmids of JAK2 were conducted. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazoliumbromide) assay, Trans-well migration and Matrigel invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. We found that JAK2 mRNA was up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p < 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in plasmid samples in patients with lung adenocarcinoma. Downregulation of JAK2 inhibited the proliferation, migration and invasion abilities of lung adenocarcinoma A549 cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of A549 cells. Thus, the up-regulation, mutation and amplification of JAK2 detected in lung adenocarcinoma may participate in lung cancer progression by regulating cancer cells' proliferation, migration and invasion.

show abstract

JAK2 V617F mutation, multiple hematologic and non-hematologic processes: an association?

Cited by 2 publications

References 19 publications

JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death

JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death

JAK2 variations and functions in lung adenocarcinoma

Contact Info

Product

Resources

About