FANCL supports Parkin-mediated mitophagy in a ubiquitin ligase-independent manner.

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. The FA proteins have functions in genome maintenance and in the cytoplasmic process of selective autophagy, beyond their canonical roles of repairing DNA interstrand cross-links. FA core complex proteins FANCC, FANCF, FANCL, FANCA, FANCD2, BRCA1 and BRCA2, which previously had no known direct functions outside the nucleus, have recently been implicated in mitophagy.

Andrographolide as a Therapeutic Agent Against Breast and Ovarian Cancers.

Andrographolide (ANDR), isolated from , is a medicinal compound effective against infections, inflammatory disorders, and various cancers. In the present study, the effects of ANDR on NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, caspase-8-mediated apoptosis and pyroptosis, and extra cellular matrix (ECM) degradation were analyzed in A431, MDA-MB231, and SKOV-3 cell lines. Results showed that ANDR inhibited the growth and proliferation of cancer cell lines by inhibiting NFkB signaling.

Mechanics of PAK1-A new molecular player in the arena of skin cancer.

Despite regular exposure of skin to solar UV-B irradiation, most individuals enjoy cancer-free existence, which is a testimony of the inherent capacity of human keratinocytes to either repair or restore cells damged by UV exposure. In this manuscript, we focus on delineating the mechanistic role of p21 activated kinase (Pak1) in UV-B provoked skin lesions. Molecular mechanistic studies revealed that Pak1 is triggered as a consequence to UV-B exposure via epidermal growth factor receptor (EGFR) and cyclobutane pyrimidine dimers (CPD) pathways, and both these membranous (EGFR) and nuclear (CPDs) events converge at Pak1 activation and contribute in a coordinated manner for yielding a complete response to UV-B via upregulating Ataxia-Telangiectasia and Rad3 related (ATR).

Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry.

P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer.

Background: Therapeutic resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) is attributed to various cellular mechanisms and signaling molecules that influence as a single factor or in combination.

Design: In this study, utilizing in vitro p21-activated kinase 1 (Pak1) overexpression and knockdown cell line models along with in vivo athymic mouse tumor xenograft models and clinical samples, we demonstrate that Pak1 is a crucial signaling kinase in gemcitabine resistance.

Results: Pak1 kindles resistance via modulation of epithelial-mesenchymal transition and activation of pancreatic stellate cells.