Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most frequently diagnosed cancers in humans, however, their exact pathogenesis is not fully understood. In recent years, it has been hypothesized that the recently discovered Hippo pathway could play a detrimental role in cutaneous carcinogenesis, but no direct connections have been made. The Hippo pathway and its effector, YAP, are responsible for tissue growth by accelerating cell proliferation, however, YAP upregulation and overexpression have also been reported in numerous types of tumors. There is also evidence that disrupted YAP/Hippo signaling is responsible for cancer growth, invasion, and metastasis. In this short review, we will explore whether the Hippo pathway is an important regulator of skin carcinogenesis and if it could be a promising target for future therapies.

The diagnosis and monitoring of progressive multiple sclerosis (PMS) require further development of fast and effective clinical tools. Relations between MRI-based brain atrophy measures and cognitive impairment in people with primary progressive and secondary progressive MS (PwPPMS, n = 20 and PwSPMS, n = 19, respectively) were investigated in a prospective study with follow-up after a mean 14.97 ± 4.67 months. MRI analysis showed that at baseline and follow-up in PwSPMS, the left thalamic fraction and corpus callosum fraction were significantly lower than in PwPPMS (baseline: 0.39 ± 0.04 vs. 0.44 ± 0.06, p = 0.0203 and 0.26 ± 0.05 vs. 0.30 ± 0.05, p = 0.0097; respectively and follow-up: 0.40 ± 0.04 vs. 0.44 ± 0.07, p = 0.0443 and 0.25 ± 0.06 vs. 0.30 ± 0.05, p = 0.0103, respectively). In contrast, only at baseline, PwPPMS had a significantly lower cerebellar white matter fraction (CWMF) than PwSPMS (1.83 ± 0.20 vs. 2.01 ± 0.24, p = 0.0132). No other significant differences were observed in the MRI fractions at either study time point or in the changes of the MRI fractions between the PwPPMS and PwSPMS. However, a significant decline in the right putaminal fraction was found during observation in PwSPMS (0.332% ± 0.05% vs. 0.328% ± 0.05%, p = 0.0479). Cognitive test scores and their changes did not differ significantly between the subgroups. Declines in the Brief Visuospatial Memory Test Revised in the whole PMS group (18.74 ± 7.43 vs. 17.03 ± 7.61, p = 0.0209) and in PwPPMS (19.50 ± 8.29 vs. 17.20 ± 7.72, p = 0.0338), as well as in the Brief International Cognitive Assessment for Multiple Sclerosis in PwPPMS (1.05 ± 0.89 vs. 1.25 ± 1.02, p = 0.0421), were observed. In both PwPMS and PwPPMS, a worsening on the Symbol Digit Modalities Test (SDMT) was associated with the reduction of fractions of white matter, cerebellum and right thalamus. SDMT performance also correlated with both gray matter fraction (GMF) and CWMF in the whole group, and with cerebellar gray matter fraction (CGMF) in PwPPMS. In PwSPMS, only Stroop Color and Word Test scores correlated with GMF and CGMF. In conclusion, subtle differences between PwPPMS and PwSPMS were detected both in MRI and neuropsychological parameters. Thus, our results indicate the need for a multicomponent attempt in characterizing progression in different clinical courses of MS.

Despite significant efforts, there is still an existing need to identify diagnostic tools that would enable fast and reliable detection of the progressive stage of multiple sclerosis (MS) and help in monitoring the disease course and/or treatment effects. The aim of this prospective study in a group of people with progressive MS was to determine whether changes in the levels of selected serum biomarkers and in cognitive function may predict disease progression, and therefore refine the decision-making process in the evaluation of MS patients. Forty two (42) patients with progressive MS completed all the study procedures; the mean duration of follow-up was 12.97 months. During the observation period, serum concentration of chitinase-3 like-protein-1 (CHI3L1/YKL-40) decreased significantly in the whole study group (from 4034.95 ± 262.62 to 2866.43 ± 173.37; p = 0.0005), as well as in subgroups of people with secondary progressive and primary progressive MS (SPMS: from 3693.81 ± 388.68 to 2542.76 ± 256.59; p = 0.0207; and PPMS: from 4376.09 ± 353.27 to 3190.09 ± 233.22; p = 0.0089, respectively). A significant worsening of Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) scores was detected in the whole study group (from 1.18 ± 0.14 to 1.34 ± 0.15; p = 0.0331) as well as in the PPMS subgroup (from 1.04 ± 0.18 to 1.26 ± 0.20; p = 0.0216). No correlations between the analyzed molecular parameters or the results of neuropsychological tests and physical disability were observed. In conclusion, an emphasis should be placed on furthering the search for multimodal biomarkers of disease progression, especially in the PMS population, based on simultaneous analysis of several factors, such as blood biomarkers and cognitive profiles.

Background: The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation by ultraviolet radiation has not been described thoroughly. In order to address this issue, we focused on how different doses of ultraviolet B affect Hippo signaling pathway components and its upstream regulators, JNK1/2 and ABL1, in human keratinocytes. Additionally, we decided to determine how silencing of YAP influences Hippo pathway component expression. Methods: Primary epidermal keratinocytes were irradiated using UVB lamps with increasing doses of ultraviolet B radiation (including 311 nm UVB). Real-time PCR was used to determine the mRNA levels of each investigated gene. The experiment was then performed after YAP silencing using siRNA transfection. Additionally, we determined the mRNA expression of Hippo pathway components in an A431 cSCC cell line. Results: We observed that YAP mRNA expression in the A431 cell line was insignificant in comparison to control, while in the case of LATS1/2, a significant increase was noted. UVB irradiation did not change the levels of YAP mRNA expression in human epidermal keratinocytes. LATS1, LATS2, ABL1 and MAP4K4 mRNA expression was significantly upregulated after UVB irradiation in non-YAP-silenced keratinocytes in a dose-dependent manner, while after YAP silencing, only LATS2 and ABL1 showed significant mRNA upregulation. The 311 nm UVB irradiation resulted in significant, dose-dependent mRNA upregulation in non-YAP-silenced keratinocytes for LATS1, ABL1 and MAP4K4. After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. Conclusions: YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP.