The cJUN NH2-terminal kinase (JNK) pathway contributes to mouse mammary gland remodeling during involution

Involution returns the lactating mammary gland to a quiescent state after weaning. The mechanism of involution involves collapse of the mammary epithelial cell compartment. To test whether the cJUN NH2-terminal kinase (JNK) signal transduction pathway contributes to involution, we established mice with JNK deficiency in the mammary epithelium. We found that JNK is required for efficient involution. JNK deficiency did not alter the STAT3/5 or SMAD2/3 signaling pathways that have been previously implicated in this process. Nevertheless, JNK promotes the expression of genes that drive involution, including matrix metalloproteases, cathepsins, and BH3-only proteins. These data demonstrate that JNK has a key role in mammary gland involution post lactation

The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation

Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent loss-of-function mutations in components of the cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor suppressive function was not mediated by a role of JNK in the growth of established tumors, but by a requirement of JNK to prevent tumor initiation. Together, these data identify JNK pathway defects as \u27driver\u27 mutations that promote genome instability and tumor initiation

Hispanics have the lowest stem cell transplant utilization rate for autologous hematopoietic cell transplantation for multiple myeloma in the United States: A CIBMTR report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138212/1/cncr30747_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138212/2/cncr30747.pd

E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer

Human papillomaviruses (HPV) are a major cause of malignancy worldwide, contributing to ~5% of all human cancers including almost all cases of cervical cancer and a growing number of ano-genital and oral cancers. HPV-induced malignancy is primarily driven by the viral oncogenes, E6 and E7, which manipulate host cellular pathways to increase cell proliferation and enhance cell survival, ultimately predisposing infected cells to malignant transformation. Consequently, a more detailed understanding of viral-host interactions in HPV-associated disease offers the potential to identify novel therapeutic targets. Here, we identify that the c-Jun N-terminal kinase (JNK) signalling pathway is activated in cervical disease and in cervical cancer. The HPV E6 oncogene induces JNK1/2 phosphorylation in a manner that requires the E6 PDZ binding motif. We show that blockade of JNK1/2 signalling using small molecule inhibitors, or knockdown of the canonical JNK substrate c-Jun, reduces cell proliferation and induces apoptosis in cervical cancer cells. We further demonstrate that this phenotype is at least partially driven by JNK-dependent activation of EGFR signalling via increased expression of EGFR and the EGFR ligands EGF and HB-EGF. JNK/c-Jun signalling promoted the invasive potential of cervical cancer cells and was required for the expression of the epithelial to mesenchymal transition (EMT)-associated transcription factor Slug and the mesenchymal marker Vimentin. Furthermore, JNK/c-Jun signalling is required for the constitutive expression of HPV E6 and E7, which are essential for cervical cancer cell growth and survival. Together, these data demonstrate a positive feedback loop between the EGFR signalling pathway and HPV E6/E7 expression, identifying a regulatory mechanism in which HPV drives EGFR signalling to promote proliferation, survival and EMT. Thus, our study has identified a novel therapeutic target that may be beneficial for the treatment of cervical cancer

Apie sovietmečio Lietuvą, savaimią visuomenę ir Sąjūdį : recenzija

„Sąjūdžio ištakų beieškant: nepaklusniųjų tinklaveikos galia“ (2012) (sud. Jūratė Kavaliauskaitė ir Ainė Ramonaitė) – daug privalumų turinti knyga, bet recenzijoje apsiribosiu kritiškomis pastabomis. Didžiausias knygos privalumas tas, kad įtikinamai parodoma, jog Lietuvos visuomenė buvo įvairesnė ir įdomesnė negu įprastai vaizduojama(si). Pažymima, kad aprašant šį laikotarpį, dažnai užmirštama, jog greta privataus gyvenimo ir oficiozinių viešųjų institutų būta kitų socialumo formų, erdvių, to, kas knygoje vadinama savaimia visuomene. Pagrindinė tyrimo tezė – Sąjūdžiui atsirasti buvo reikalingi savaimios visuomenės tinklai kaip palankiausia dirva bręsti režimo opozicijai – yra ir ambicinga, ir gana kukli. Viena vertus, Sąjūdžio genezę siūloma traktuoti kaip antitotalitarizmo, o ne valstybingumo ar kovos su imperija istoriją, kaip yra įprasta. Kita vertus, knygoje stinga aiškių priklausymo savaimiai visuomenės kriterijų, jos ribų apibrėžimo. Manau, jog savaimi visuomenė buvo būtina, bet ne pakankama sąlyga Sąjūdžiui atsirasti. Be politinių ir geopolitinių aplinkybių analizės lieka neaišku, kaip politiškai paklusni 1986 m. Lietuva pavirto 1988 m. maištininke. Atribojimas nuo ankstesnių aiškinimų nėra absoliutus, nes iki galo nepaaiškinama, kaip savaimios visuomenės noras gyventi savaip ir pokyčių troškimas peraugo į nepriklausomybės siekį. Pagrindinis knygos duomenų šaltinis – pokalbiai su dalyviais, tačiau dalyvių atrankos principus, o taip pat pačius atsiminimus, kaip ir visus dokumentus, reikia vertinti atsargiai