{"title":"Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display","authors":"Leah E. Knepper, Emily T. Ankrom, Damien Thévenin","doi":"10.1007/s00232-024-00322-3","DOIUrl":"https://doi.org/10.1007/s00232-024-00322-3","url":null,"abstract":"<p>One of the main challenges with many cancer immunotherapies is that biomarkers are needed for targeting. These biomarkers are often associated with tumors but are not specific to a particular tumor and can lead to damage in healthy tissues, resistance to treatment, or the need for customization for different types of cancer due to variations in targets. A promising alternative approach is to target the acidic microenvironment found in most solid tumor types. This can be achieved using the pH (Low) Insertion Peptide (pHLIP), which inserts selectively into cell membranes under acidic conditions, sparing healthy tissues. pHLIP has shown potential for imaging, drug delivery, and surface display. For instance, we previously used pHLIP to display epitopes on the surfaces of cancer cells, enabling antibody-mediated immune cell recruitment and selective killing of cancer cells. In this study, we further explored this concept by directly fusing an anti-CD16 nanobody, which activates natural killer (NK) cells, to pHLIP, eliminating the need for antibody recruitment. Our results demonstrated the insertion of pH-sensitive agents into cancer cells, activation of the CD16 receptor on effector cells, and successful targeting and destruction of cancer cells by high-affinity CD16<sup>+</sup> NK cells in two cancer cell lines.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":518001,"journal":{"name":"The Journal of Membrane Biology","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chewon Yim, Yeonji Chung, Sungjoon Son, Jeesoo Kim, Jong-Seo Kim, Hyun Kim
{"title":"Abundance of the Membrane Proteome in Yeast Cells Lacking Spc1, a Non-catalytic Subunit of the Signal Peptidase Complex","authors":"Chewon Yim, Yeonji Chung, Sungjoon Son, Jeesoo Kim, Jong-Seo Kim, Hyun Kim","doi":"10.1007/s00232-024-00312-5","DOIUrl":"https://doi.org/10.1007/s00232-024-00312-5","url":null,"abstract":"<p>The signal peptidase complex (SPC) mediates processing of signal peptides of secretory precursors. But, recent studies show that the eukaryotic SPC also cleaves internal transmembrane segments of some membrane proteins, and its non-catalytic subunit, Spc1/SPCS1 plays a critical role in this process. To assess the impact of Spc1 on membrane proteostasis, we carried out quantitative proteomics of yeast cells with and without Spc1. Our data show that the abundance of the membrane proteome in yeast cells lacking Spc1 is in general reduced compared to that in wild-type cells, implicating its role in controlling the cellular levels of membrane proteins.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":518001,"journal":{"name":"The Journal of Membrane Biology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond Hormones: Investigating the Impact of Progesterone Receptor Membrane Component 1 in Lung Adenocarcinoma","authors":"","doi":"10.1007/s00232-024-00311-6","DOIUrl":"https://doi.org/10.1007/s00232-024-00311-6","url":null,"abstract":"<h3>Abstract</h3> <p>Progesterone Receptor Membrane Component 1 (<em>PGRMC1</em>) is a candidate oncogene with a prominent involvement in the pathogenesis of diverse cancers (ovarian, thyroid, breast, colon, head, and neck). Our study ascertains the ability of <em>PGRMC1</em> to influence <em>WNT</em> members in the non-small cell lung cancer subtype-lung adenocarcinoma (LUAD) and participates in augmented cell proliferation and migration. Both computational and in vitro experimental analyses were performed in this study. Gene silencing, in vitro assays, gene expression & and protein expression studies were performed to ascertain the role of <em>PGRMC1</em> in LUAD cells. The computational analysis, <em>PGRMC1</em> gene level expression was analysed using the microarray gene expression omnibus datasets (GSE27262; GSE18842) to compare LUAD tumours and normal tissues. Concurrently, the gene expression profiling interactive analysis of <em>PGRMC1 and</em> Kaplan–Meier survival analysis revealed a decreasing patient survival rate with an increasing PGRMC1 gene expression in LUAD tumour samples. Interestingly, the experimental gene silencing studies were conducted in vitro (si-PGRMC1 Vs si-Control) to understand the essential role of <em>PGRMC1</em> in regulating <em>WNT</em>-associated genes (<em>WNT1, WNT5A,</em> and <em>WNT11</em>). Comparative experimental cell migration and spheroid formation assays (si-PGRMC1 Vs si-Control) in vitro showed a strong association between <em>PGRMC1</em> and LUAD. In vitro expression analysis using real-time PCR and western blot further confirmed the connecting link between <em>PGRMC1</em> and <em>WNT5A</em> compared to other <em>WNT</em> member genes (<em>WNT1</em> and <em>WNT11</em>) in LUAD. The computational and experimental analyses agreed with one another.</p> <span> <h3>Graphical Abstract</h3> <p> <span> <span> <img alt=\"\" src=\"https://static-content.springer.com/image/MediaObjects/232_2024_311_Figa_HTML.png\"/> </span> </span></p> </span>","PeriodicalId":518001,"journal":{"name":"The Journal of Membrane Biology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}