SOX11 regulates expression of Xist in a cell type specific manner.

We demonstrate here diverse nuclear and developmental functions of Sox11 including control of the non-coding RNA that functions in developmentally programmed and homeostatic gene regulation by dosage compensation and expression regulation of the of lin complexes functioning in embryonic development and stem cell biology, including lin-7, lin-9b and lin-54. This appeared to be a reciprocal relationship, with Xist controlling homeobox expression, like Xist regulation of brain-specific GBX2 in the lung, where GBX2 expression distinguished the adeno and squamous subtypes of NSCLC. We observed homeobox control of Xist, including Sox11 dependent control of Xist, ILF3, and exclusive regulation of BAZ1A/BAZ1B and BAZ2B expression, as well as Xist-associated CIZ1 and hnRNPdl/hnRNPA0. Together, we found SOX11 supported metastasis to the CNS by a variety of methods which we demonstrate strate here included cell-type specific control of Xist and include facilitating subtype selection of a subtype that is intrinsically biased towards CNS metastasis, through modulating the HER2 CNS locus including genes important for survival of humans with breast cancer following metastasis to the CNS through supporting CNS colonization by an identify principle, enhancing and controlling expression of CNS-restricted genes, through facilitating metastasis through the EMT and CSC/CTC associated programs, supporting transformation generally (clinically appreciated as resistance or recurrence) through controlling expression of CDK12 and E2F gene expression, potential effects through modulating tumor suppressor function through Nf1/2, facilitating immune evasion in the immunologically restricted CNS through class II silencing and modulation of senescence program genes that have immunologic functions like TOX2, CTLA4, Pd Cd1lg2 and AHR, and through specific regulation of HER2 subtype selection by controlling expression of genes important for HER2 and hormone receptor positive cancer, including the ESR1 co-factor GREB1, cell type dependent control of ERBB2 itself, and modulation of HER1-4 expression regulation during clonal selection and in the tumor at steady state (other ERBB family genes) including EGFR, ERBB3, and ERBB4.