Biochemistry and Molecular Biology Discipline

Center for Proteomics and Molecular Therapeutics

Dr. Erin N. Howe received her PhD in Cancer Biology from the University of Colorado as an NIH/NCI NRSA Graduate Fellow. She was then a NIH/NCATS TL1 and NIH/NCI NRSA Postdoctoral Fellow at the University of Notre Dame and Harper Cancer Research Institute.

The lifetime risk of developing breast cancer is 1 in 8 for American women, and metastasis is responsible for over 90% of breast cancer related morbidity and mortality. We focus on dissecting the molecular mechanisms driving metastatic breast cancer, where we recently identified endosomal recycling as a mechanism driving breast cancer adaptation to the brain metastatic microenvironment. We showed that Rab11b-mediated recycling of integrin beta 1 allows breast cancer cells to adhere and proliferate in the brain. Inhibition of Rab11b recycling reverses this, substantially decreasing brain metastasis and increasing survival. We are building on this finding to ask how the metastatic microenvironment alters endosomal recycling, and how recycling regulates cancer-immune interactions in the metastatic niche. Ultimately, understanding how cancer cells interact with the metastatic niche and evade the immune system will identify novel therapeutic options and next-generation immunotherapies for patients with devastating breast cancer metastases. This work has been supported by the NIH/NCI, American Cancer Society, and the METAvivor Foundation.

Publications

• Palakurthi B, Fross SR, Guldner IH, Aleksandrovic E, Liu X, Martino AK, Wang Q, Neff RA, Golomb SM, Lewis C, Peng Y, Howe EN, Zhang S. Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer. Nat Commun. 2023 Apr 13;14(1):2109. doi: 10.1038/s41467-023-37727-y. PMCID: PMC10101955.
• Bahcecioglu G, Yue X, Howe EN, Guldner IH, Stack MS, Zhang S, Zorlutuna P. Aged breast extracellular matrix drives mammary epithelial cells to an invasive and cancer-like phenotype. Advanced Science. 7 October 2021. PMID: 34617419.
• Guldner IH, Wang Q, Yang L, Golomb SM, Zhao Z, Lopez JA, Brunory A, Howe EN, Zhang Y, Palakurthi B, Barron M, Gao H, Xuei X, Liu Y, Li J, Chen DZ, Landreth GE, Zhang S. CNS-native myeloid cells drive immune suppression in the brain metastatic niche through Cxcl10. Cell. 27 October 2020. PMID: 33113353.
• Howe EN, Burnette MD, Justice ME, Schnepp PM, Hendrick V, Clancy JW, Guldher IH, Lamere AT, Li J, Aryal UK, D’Souza-Schorey C, Zartman JJ, Zhang S*. Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth. Nature Communications, 15 June 2020. PMCID: PMC7295786.
• Rodriguez KX, Howe EN, Bacher EP, Burnette MD, Meloche JL, Meisel J, Schnepp P, Tan X, Chang M, Zartman J, Zhang S, Ashfeld BL. Combined scaffold evaluation and systems-level transcriptome-based analysis for accelerated lead optimization reveals ribosomal targeting spirooxindole cyclopropanes. ChemMedChem, 29 May 2019. PMID: 31140738.
• Ni YJ, Schmidt KR, Werner BA, Koenig JK, Guldner IH, Schnepp PM, Tan X, Jiang L, Host M, Sun L, Howe EN, Wu J, Littlepage LE, Nakshatri H, Zhang S. Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer. Nature Communications, 28 June 2019. PMID: 31253784.
• Schnepp PM, Lee DD, Guldner IH, O’Tighearnaigh TK, Howe EN, Palakurthi B, Eckert KE, Toni TA, Ashfeld BL, Zhang S. GAD1 upregulation programs aggressive features of cancer cell metabolism in the brain metastatic microenvironment. Cancer Research, 1 June 2017. PMCID: PMC5461057.
• Zellmer VR, Schnepp PM, Fracci SL, Tan X, Howe EN, Zhang S. Tumor-induced stromal STAT1 accelerates breast cancer via deregulating tissue homeostasis. Molecular Cancer Research, 20 Jan. 2017. PMCID: PMC5415415.
• Wahdan-Alaswad RS, Cochrane DR, Spoelstra NS, Howe EN, Edgerton SM, Anderson SM, Thor AD, Richer JK. Metformin-induced killing of triple-negative breast cancer cells is mediated by reduction in fatty acid synthase via miRNA-193b. Hormones and Cancer, 12 Sep. 2014. PMID: PMC4570735.
• Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gomez F, Medicherla S, Alfaro IE, McCullagh E, Jedlicka P, Torkko KC, Thor AD, Elias AD, Protter AA, and Richer JK. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Research, 2014. PMCID: PMC3978822.
• Howe EN, Cochrane DR, Cittelly DM and Richer JK. miR-200c targets a TrkB/NTF3 autocrine signaling loop to suppress anoikis resistance in breast cancer. PLoS ONE, 2012 Nov 21. PMCID: PMC3503774.
• D’Amato NC, Howe EN and Richer JK. MicroRNA Regulation of Epithelial Plasticity in Cancer. Cancer Letters, invited review, 2012 Dec 7. PMID: 23228634.
• Cittelly DM, Dimitrova I, Howe EN, Cochrane DR, Jean A, Broaddus RR, Spillman MA and Richer JK. Restoration of miR-200c to ovarian cancer reduces tumor burden and increases sensitivity to paclitaxel. Molecular Cancer Therapeutics, 2012 Oct 16. PMCID: PMC3519949.
• Cittelly DM, Finlay-Schultz J, Howe EN, Spoestra N, Axlund S, Hendricks P, Jacobsen BM, Sartorius CA and Richer JK. Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4. Oncogene, 2012 Jul 2. DOI: 10.1038/onc.2012.275. PMCID: PMC4236860.
• Howe EN, Cochrane DR and Richer JK. The miR-200 and miR-221/222 miRNA Families: Opposing Effect on Epithelial Identity. Journal of Mammary Gland Biology and Neoplasia, invited review. DOI: 10.1007/s10911-012-9244-6. PMCID: PMC4561555.
• Cochrane DR, Jacobsen BM, Howe EN, Bain DL and Richer JK. Progestin Regulated miRNAs that Mediate Progesterone Receptor Action in Breast Cancer. Molecular and Cellular Endocrinology, May 2012. PMCID: PMC4716679.
• Howe EN, Cochrane DR and Richer JK. Targets of miR-200c Mediate Suppression of Cell Motility and Anoikis Resistance. Breast Cancer Research, 2011 Apr 18;13(2):R45. PMCID: PMC3219208.
• Cochrane DR, Cittelly DM, Howe EN, Spoelstra NS, McKinsey EL, LaPara K, Elias A, Yee D and Richer JK. MicroRNAs Link Estrogen Receptor Alpha Status and Dicer Levels in Breast Cancer. Hormones and Cancer. DOI: 10.1007/s12672-010-0043-5. PMCID: PMC4561556.
• Cochrane DR, Howe EN, Spoelstra NS and Richer JK. Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers. J Oncol. 2010;2010:821717. PMCID: PMC2798671.
• Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c Mitigates Invasiveness and Restores Sensitivity to Microtubule-Targeting Chemotherapeutic Agents. Mol Cancer Ther 2009; 8(5):1055-1066. PMCID: PMC4573391.
• Singh M, Spoelstra NS, Jean A, Howe EN, Darling D, Shroyer S, Broaddus RR, and Richer JK. ZEB1 Expression in Type 1 versus Type 2 Endometrial Cancers. Modern Pathology 2008 Jul;21(7):912-23. PMID: 18487993.