TY - JOUR T1 - Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin. JF - Cell Rep Y1 - 2022 A1 - Badarinath, Krithika A1 - Dam, Binita A1 - Kataria, Sunny A1 - Zirmire, Ravindra K A1 - Dey, Rakesh A1 - Kansagara, Gaurav A1 - Ajnabi, Johan A1 - Hegde, Akshay A1 - Singh, Randhir A1 - Masudi, Tafheem A1 - Sambath, Janani A1 - Sachithanandan, Sasikala P A1 - Kumar, Prashant A1 - Gulyani, Akash A1 - He, You-Wen A1 - Krishna, Sudhir A1 - Jamora, Colin KW - Carcinoma, Squamous Cell KW - Cell Line, Tumor KW - Epithelial Cells KW - Extracellular Matrix Proteins KW - Humans KW - Integrins KW - Neoplasm Proteins KW - Neoplasm Recurrence, Local KW - Neoplastic Stem Cells KW - Skin Neoplasms KW - Snail Family Transcription Factors AB -

Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes. Snail-expressing cells secrete the matricellular protein Mindin, which functions in an autocrine fashion to activate a Src-STAT3 pathway to reinforce their stem/progenitor phenotype. This pathway is activated by the engagement of Mindin with the leukocyte-specific integrin, CD11b (ITGAM), which is also unexpectedly expressed by epidermal keratinocytes. Interestingly, disruption of this signaling module in human cSCC attenuates tumorigenesis, suggesting that targeting Mindin would be a promising therapeutic approach to hinder cancer recurrence.

VL - 40 IS - 12 ER - TY - JOUR T1 - FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation. JF - iScience Y1 - 2018 A1 - D'Souza, Michelle Ninochka A1 - Gowda, Naveen Kumar Chandappa A1 - Tiwari, Vishal A1 - Babu, Rosana Ottakandathil A1 - Anand, Praveen A1 - Dastidar, Sudhriti Ghosh A1 - Singh, Randhir A1 - James, Owen G A1 - Selvaraj, Bhuvaneish A1 - Pal, Rakhi A1 - Ramesh, Arati A1 - Chattarji, Sumantra A1 - Chandran, Siddharthan A1 - Gulyani, Akash A1 - Palakodeti, Dasaradhi A1 - Muddashetty, Ravi S AB -

FMRP is an RNA-binding protein that is known to localize in the cytoplasm and in the nucleus. Here, we have identified an interaction of FMRP with a specific set of C/D box snoRNAs in the nucleus. C/D box snoRNAs guide 2'O methylations of ribosomal RNA (rRNA) on defined sites, and this modification regulates rRNA folding and assembly of ribosomes. 2'O methylation of rRNA is partial on several sites in human embryonic stem cells, which results in ribosomes with differential methylation patterns. FMRP-snoRNA interaction affects rRNA methylation on several of these sites, and in the absence of FMRP, differential methylation pattern of rRNA is significantly altered. We found that FMRP recognizes ribosomes carrying specific methylation patterns on rRNA and the recognition of methylation pattern by FMRP may potentially determine the translation status of its target mRNAs. Thus, FMRP integrates its function in the nucleus and in the cytoplasm.

VL - 9 ER -