Chronic beryllium disease (CBD) is a debilitating pulmonary disorder that occurs due to persistent exposure to beryllium (Be) particles in the workplace. Be-exposure causes activation of the innate immune system, resulting in the secretion of interleukins and chemokines that drive the accumulation of B and T cells in the lungs. However, the mechanisms by which innate molecules influence the recruitment of B cells and B cell-mediated protection in CBD are poorly understood. In this study, we employed multiple approaches to examine the role of innate immune signaling and CD4+ T cells in B cell recruitment and function in the lungs. We show that the absence or blocking of IL-1R1 signaling prevents the recruitment of B cells to the lungs of BeO-exposed mice. Additionally, we show that B cell recruitment to the lungs depends on the chemokine receptor, CXCR5, and CD4+ T cells. In BeO-exposed mice, lung B cells down-regulate IgM but showed an increased IgD and CD44 surface expression. Further, RNA sequencing of pulmonary tissue-specific B cells in CBD revealed distinct gene signatures compared to splenic B cells, with increased expression of pathways involved in antigen presentation, tight junction interactions, and interferon signaling. Overall, our study shows that B cell recruitment and aggregate formation during CBD depend on sequential activation of innate and adaptive immune responses.

Abstract Introduction: Microtubule-associated proteins (MAPs) regulate microtubule dynamics, which is critical for controlling cell division, proliferation, migration, and intracellular transport. Due to their critical role in maintaining cellular integrity, microtubules have served as potent therapeutic targets for cancer treatment. Here, we report “Matrin 3 (MATR3)” as a novel MAP that interacts with β- tubulin and γ-tubulin, which constitutes microtubule organizing center (MTOC) essential for proper spindle formation and chromosomal segregation. Methods: Breast cancer cell lines (MDA-MB-231, MDA-MB-468, SKBR3, MCF7, BT549, HMEC, and MCF10A) were purchased from the American Type Culture Collection and cultured in standard medium. Breast cancer cells were transfected either with MATR3 overexpression plasmid or siRNA specific to MATR3. These overexpression/knockdown breast cancer cells were analyzed for cell viability, migration, invasion, colony formation, cell cycle, apoptosis assays, RNA sequencing, RT-qPCR, western blotting, RNA immunoprecipitation, and in vivo tumor xenograft study. Results: Our findings show that MATR3 binds to RNA encoding MAPs including β-tubulin and γ-tubulin, and regulate their stabilization. MATR3 also interacted with β-tubulin protein. Our data demonstrate that MATR3 functions as a tumor suppressor, as its overexpression inhibits cancer growth, while its depletion increased tumor growth in vivo. Mechanistic studies confirmed that MATR3 mediates its tumor suppressor role by regulating the expression of the MTOC-associated protein-encoding gene MZT2B (Mitotic Spindle Organizing Protein 2B), which is overexpressed in cancers and promotes cancer growth. Further, loss of MATR3 expression or function results in dysregulated microtubule dynamics and uncontrolled expression of the oncogenic proteins including MZT2B. Conclusions: In conclusion, our data strongly suggests that MATR3 serves as a novel RNA-binding protein with tumor suppressor properties. This discovery holds significant importance as MATR3 becomes the second protein, following Adenomatous Polyposis Coli (APC), to be identified for its binding to both MAP RNA and protein. Citation Format: Panneerdoss Subbarayalu, Subapriya Rajamanickam, Santosh Timilsina, Saif Nirzhor, Daisy Medina, Shahad Abdulsahib, Pitta V Prabhakar, Deepika Singh, Fu-Yang Li, Pooja Yadav, Esha Reddy, Krishna Evani, Vijay Eedunuri, Trong Phat Do, Benjamin C. Onyeagucha, Tabrez A. Mohammad, Jae-Hoon Ji, Yidong Chen, Nourhan Abdelfattah, Nicholas Dybdal-Hargreaves, Li-Ju Wang, Yu-Chiao Chiu, Suryavathi Viswanadhapalli, Ratna K. Vadlamudi, Manjeet K. Rao. RNA binding protein Matrin3 acts as a tumor suppressor by inhibiting microtubule nucleation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 628.

The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive. In contrast to chemotherapy drugs, systemic delivery of CB suppressed breast cancer growth and metastasis with no toxicity in pre-clinical mouse models. Using PDX and ex vivo explants from estrogen receptor (ER) positive, ER mutant and TNBC patients, we further demonstrated that CB effectively blocks therapy-sensitive and therapy-resistant breast cancer growth without affecting normal breast tissue. Our data provide a strong rationale to develop CB as a viable therapeutic for treating breast cancers.

Despite improvement in overall survival, many patients with breast cancers still succumb to this disease. Identification of new biomarkers and safe therapeutic targets are urgently needed to improve the overall clinical outcome of breast cancer patients. Our studies discovered a RNA binding protein, MATRIN3 (MATR3), as a novel tumor suppressor. MATR3 is expressed at a significantly reduced levels in breast tumors. MATR3 inhibited short and long-term viability as well as migration and invasion of breast cancer cells. Further, MATR3 overexpression suppressed tumor growth, while its depletion induced tumor growth in orthotopic mouse tumor models. RNA seq and RNA immunoprecipitation analyses revealed that MATR3 binds and directly regulates the expression of several microtubule-associated proteins. Mechanistic studies identified MZT2B, a mitotic spindle organizing protein as a down stream effector of MATR3. MZT2B knockdown or knockout using CRISPR-CAS9 resulted in significantly decreased short and long term viability as well as reduced migration and invasion of breast cancer cells. Notably, MZT2B overexpression rescued the inhibitory effect of MATR3 overexpression on breast cancer growth. Furthermore, MATR3 overexpression downregulated expression of key microtubule nucleation protein complex including γ-tubulin and γ-tubulin ring complex protein (TUBGCP). Our data suggest that MATR3 inhibits breast cancer growth and progression by inhibiting MZT2B and consequently microtubule nucleation in breast cancers. Citation Format: Panneerdoss Subbarayalu, Subapriya Rajamanickam, Suryavathi Viswanadhapalli, Fuyang Li, Vijay Eedunuri, Pooja Yadav, Esha Reddy, Santosh Timilsina, Saif SR Nirzhor, Benjamin C Onyeagucha, Li-Ju Wang, Yu-Chiao Chiu, Tabrez Mohammad, Nourhan Abdelfattah, Nicholas Dybdal-Hargreaves, Yidong Chen, Ratna Vadlamudi, Manjeet Rao. Matrin3 inhibits breast cancer growth by suppressing microtubule nucleation protein MZT2B [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-14.

Cancer cell lines serve as invaluable model systems for cancer biology research and help in evaluating the efficacy of new therapeutic agents. However, cell line contamination and misidentification have become one of the most pressing problems affecting biomedical research. Available methods of cell line authentication suffer from limited access, time-consuming and often costly for many researchers, hence a new and cost-effective approach for cell line authentication is needed. In this regard, we developed a new method called CeL-ID for cell line authentication using genomic variants as a byproduct derived from RNA-seq data. CeL-ID was trained and tested on publicly available more than 900 RNA-seq dataset derived from the Cancer Cell Line Encyclopedia (CCLE) project; including most frequently used adult and pediatric cancer cell lines. We generated cell line specific variant profiles from RNA-seq data using our in-house pipeline followed by pair-wise variant profile comparison between cell lines using allele frequencies and depth of coverage values of the entire variant set. Comparative analysis of variant profiles revealed that they differ significantly from cell line to cell line whereas identical, synonymous and derivative cell lines share high variant identity and their allelic fractions are highly correlated, which is the basis of this cell line authentication protocol. Additionally, CeL-ID also includes a method to estimate the possible cross-contamination using a linear mixture model with any possible CCLE cells in case no perfect match was detected.

Abstract The development of novel targeted therapies is urgently required for improving the outcome of breast cancer patients. Chemotherapy is the common treatment option for malignant breast cancer. However, resistance and toxicity remain the major obstacles hindering the effectiveness of chemotherapeutic agents in cancer patients. Therefore, identifying genes/factors that sensitize breast cancer cells to chemotherapeutic agents could improve treatment outcome in patients. Using an unbiased high-throughput screen, we identified Signal peptide CUB domain EGF-like 3 (SCUBE3) genes as a novel therapeutic adjuvant that can improve the efficacy of doxorubicin, a chemotherapeutic agent commonly used in treating breast cancer patients. Our findings demonstrated that SCUBE3 promotes breast cancer cells' progression as knockdown of SCUBE3 inhibited the ability of breast cancer cells to form colony, migrate, and invade, while overexpression of SCUBE3 promoted tumor growth in preclinical mouse models. Our results revealed that SCUBE3 mediates its protumor effects by regulating genes involved in growth and survival in the MAPK pathway, DNA damage surveillance pathway including RAD51 and FOXM1, and apoptotic pathway including Mcl-1. Using interaction studies, we demonstrated that EGFR is a true receptor of SCUBE3 as EGFR and SCUBE3 interact and this interaction mediated progrowth signaling of SCUBE3. These findings underline the importance of SCUBE3 as a potent therapeutic target for treating breast cancer patients. Citation Format: Benjamin C. Onyeagucha, Kashish Dhillon, Subapriya Rajamanickam, Subbarayalu Panneerdoss, Vijay K. Eedunuuri, Tabrez A. Mohammad, Santosh Timilsina, Yidong Chen, Manjeet K. Rao. SCUBE3 inhibition improves doxorubicin response in breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B066.

We reported that tumor intrinsic PD-L1 promotes tumor initiating cell (TIC) virulence and mTORC1. Others have focused on PI3K/AKT/mTOR in promoting TIC, but specific downstream mTOR regulators of tumor stemness are unknown. We knocked down Raptor (mTORC1 component, Rptorlo) in ID8agg cells (murine ovarian cancer). Rptorlo cells had reduced mTORC1 with no change in PD-L1 in total cells or CD44+CD24+ TIC. %TIC was reduced in Rptorlo cell cultures, and Rptorlo TIC were functionally defective for self-renewal by tumorosphere formation. Rapamycin (mTORC1 inhibitor) reduced ID8agg Rptor, tumorospheres, and the stemness and virulence genes Oct4 and Nanog. Oct4 knockin to PD-L1lo ID8agg restored TIC numbers and spheres. Together, data confirm PD-L1 drives stemness through Oct4 by increasing mTORC1. Rptorlo TIC formed significantly smaller tumors vs. control TIC in immunodeficient NSG mice, confirming TIC intrinsic Rptor drives immune independent virulence. In wild type mice, Rptorlo vs. control TIC produced less ascites and smaller tumors with lower %TIC in vivo (but similar PD-L1), significantly more recently-activated CD44hiCD62LloCD8+ cells in ascites and draining lymph nodes (DLN). CCR2+CD8+ T cells and CXCR5+TCF1+PD-1+Tim3− stem-like T cells were also increased in Rptorlo DLN. Thus, Rptorlo TIC influence systemic and tumor-associated immunity. In high grade serous ovarian tumors (The Cancer Genome Atlas) high Rptor expression predicted a significantly higher cancer stem cell signature, and lower median survival in late stage patients. Our work establishes tumor intrinsic Rptor driven by PD-L1 plays a key role in regulating TIC and stem like T cells and can be a prognostic marker for late stage ovarian cancer patients.

Cell lines form the cornerstone of cell-based experimentation studies into understanding the underlying mechanisms of normal and disease biology including cancer. However, it is commonly acknowledged that contamination of cell lines is a prevalent problem affecting biomedical science and available methods for cell line authentication suffer from limited access as well as being too daunting and time-consuming for many researchers. Therefore, a new and cost effective approach for authentication and quality control of cell lines is needed. We have developed a new RNA-seq based approach named CeL-ID for cell line authentication. CeL-ID uses RNA-seq data to identify variants and compare with variant profiles of other cell lines. RNA-seq data for 934 CCLE cell lines downloaded from NCI GDC were used to generate cell line specific variant profiles and pair-wise correlations were calculated using frequencies and depth of coverage values of all the variants. Comparative analysis of variant profiles revealed that variant profiles differ significantly from cell line to cell line whereas identical, synonymous and derivative cell lines share high variant identity and are highly correlated (ρ > 0.9). Our benchmarking studies revealed that CeL-ID method can identify a cell line with high accuracy and can be a valuable tool of cell line authentication in biomedical science. Finally, CeL-ID estimates the possible cross contamination using linear mixture model if no perfect match was detected. In this study, we show the utility of an RNA-seq based approach for cell line authentication. Our comparative analysis of variant profiles derived from RNA-seq data revealed that variant profiles of each cell line are distinct and overall share low variant identity with other cell lines whereas identical or synonymous cell lines show significantly high variant identity and hence variant profiles can be used as a discriminatory/identifying feature in cell authentication model.

Collaboration among writers-readers-erasers of m 6 A regulates the stability of tumor-specific genes.

Background . Compared with the well-studied 5-methylcytosine (m 5 C) in DNA, the role and topology of epitranscriptome m 5 C remain insufficiently characterized. Results . Through analyzing transcriptome-wide m 5 C distribution in human and mouse, we show that the m 5 C modification is significantly enriched at 5′ untranslated regions (5′UTRs) of mRNA in human and mouse. With a comparative analysis of the mRNA and DNA methylome, we demonstrate that, like DNA methylation, transcriptome m 5 C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m 5 C methylation is observed at CpG sites. Further analysis reveals that RNA m 5 C methylation level is positively correlated with both RNA expression and RNA half-life. We also observed that the methylation level of mitochondrial RNAs is significantly higher than RNAs transcribed from the nuclear genome. Conclusions . This study provides an in-depth topological characterization of transcriptome-wide m 5 C modification by associating RNA m 5 C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.

Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers. Interestingly, miR-296-5p also regulates the expression of anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1), which is highly expressed in breast cancers. Our results reveal that Mcl-1 and BOK constitute a regulatory feedback loop as ectopic BOK expression induces Mcl-1, whereas silencing of Mcl-1 results in reduced BOK levels in breast cancer cells. In addition, we show that silencing of Mcl-1 but not BOK reduced the long-term growth of breast cancer cells. Silencing of both Mcl-1 and BOK rescued the effect of Mcl-1 silencing on breast cancer cell growth, suggesting that BOK is important for attenuating cell growth in the absence of Mcl-1. Depletion of BOK suppressed caspase-3 activation in the presence of paclitaxel and in turn protected cells from paclitaxel-induced apoptosis. Furthermore, we demonstrate that glycogen synthase kinase (GSK3) α/β interacts with BOK and regulates its level post-translationally in breast cancer cells. Taken together, our results suggest that fine tuning of the levels of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 may decide the fate of cancer cells to either undergo apoptosis or proliferation.

Abstract Background: Triple-negative breast cancers (TNBC) are the most aggressive forms of breast cancer and almost 60% of patients with TNBCs develop chemo-resistance, leading to recurrence, poor prognosis and poor survival. TNBCs have been reported to have high levels of replication stress, which plays pivotal role in genomic instability, and therapy resistance. Targeting replication stress is an emerging approach for better TNBC treatment. Here, we evaluated the anticancer efficacy of carbazole blue (CB), a synthetic analogue of carbazole that we recently synthesized on TNBC cells growth and progression. Experimental Design: The effect of CB on breast cancer growth was assessed in vitro as well as in orthotopic mouse xenograft and PDX-models of breast cancer. In addition, the therapeutic efficacy and safety of CB was determined in long term toxicity studies in mice and also in ex-vivo explants from breast cancer patients. The mechanism of action of CB was evaluated by performing gene expression, cell cycle, apoptosis and DNA repair studies as well as proteins involved in the above mentioned mechanisms. Results: Our results demonstrated that CB inhibits short and long term viability of TNBC cells in a dose dependent manner without affecting normal mammary epithelial cells. We show that the systemic delivery of CB using nanoparticle-based delivery approach suppressed breast cancer growth without inducing toxicity in preclinical and PDX mouse models of triple negative breast cancer. Our long term toxicity studies reveled that CB treatment did not induce any toxicity in Balb/c mice. Using ex-vivo explants from breast cancer patients, we demonstrated that CB modulated breast cancer growth. Consistent with that, our results revealed that CB treatment induced G1/S cell cycle arrest and apoptosis in TNBCs. Interestingly, our gene expression analysis revealed that CB modulates expression and activity of several genes known to be involved in DNA replication and DNA repair machinery. Conclusions: Our results for the first time showed the CB can serve as a novel and potent therapeutic agent for treating breast cancer in general and TNBC in particular. These findings highlight the potential of CB to be applied as a safe regimen for treating breast cancer patients. As exploiting replication stress to treat cancer is gaining major interest, compound/s that may induce replication stress and inhibit DNA repair ability of cancer cells, has immense translational potential. Citation Format: Subapriya Rajamanickam, Kaitlyn Bates, Santosh Timilsina, JunHyoung Park, Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Kwang Hwa Jung, Edward Favours, Tabrez A. Mohammad, Hung-I Harry Chen, Benny A. Kaipparettu, Yidong Chen, Jack L. Arbiser, Manjeet K Rao. Targeting replication stress by carbazole blue- A novel strategy to treat triple negative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1116. doi:10.1158/1538-7445.AM2017-1116

Abstract Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is Bcl-2-related Ovarian Killer (BOK), which is a pro-apoptotic protein. Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p, regulates BOK expression by binding to its 3’UTR in breast cancers. Furthermore, we show that depletion of BOK by either miR-296-5p or siRNA against BOK protected breast cancer cells from undergoing paclitaxel-induced apoptosis. Interestingly, miR-296-5p also regulates the expression of Mcl-1, which is an anti-apoptotic protein and is highly expressed in breast cancers. Our results reveal that Mcl-1 is important for suppression of BOK function as ectopic BOK expression induced Mcl-1, while silencing of BOK resulted in reduced Mcl-1 levels in breast cancer cells. In addition, we show that specific silencing of Mcl-1 reduced the long-term growth of breast cancer cells, whereas BOK inhibition didn’t have any effect on the growth of breast cancer cells. Surprisingly, silencing of both Mcl-1 and BOK rescued the effect of Mcl-1 silencing on breast cancer cell growth, suggesting that BOK is important for attenuating cell growth in the absence of Mcl-1, and also showing a tight feedback regulatory loop between BOK and Mcl-1 in breast cancer cells. Furthermore, we demonstrated that BOK protein level is regulated post-translationally by GSK3α and to some extent GSK3β as GSK3 inhibitor (CHIR99021) or silencing of GSK3 significantly increased BOK protein levels in breast cancer cells. Notably, we found that Mcl-1 interacts with GSK3α/β and silencing of Mcl-1 using siRNA significantly attenuated endogenous GSK3α/β levels in breast cancer cells. Taken together, our results suggest that fine tuning (either post-transcriptionally by miR-296-5p or post-translationally by GSK3) of the levels of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 decide the fate of cancer cells to either undergo Apoptosis or proliferation. Citation Format: Benjamin Chidi Onyeagucha, Panneerdoss Subbarayalu, Subapriya Rajamanickam, Nourhan Abdelfattah, Santosh Timilsina, Rosa M. Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Hima Bansal, Tabrez A. Mohammad, Yidong Chen, Manjeet K. Rao. Novel regulatory mechanisms for Bcl2-related Ovarian Killer (BOK) expression in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2336. doi:10.1158/1538-7445.AM2017-2336

Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP. Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

Microtubule-targeting drugs are widely used as cancer chemotherapeutic agents and they have been shown to inhibit mitotic progression and interphase signaling. Despite their use as a first line treatment for cancer, many patients develop resistance to microtubule-targeting drugs leading to early relapse and shorter survival. Moreover, the quality of life for patients who do survive is often substantially reduced due to the toxicity associated with these drugs. Therefore, identification of new factors that determine the effectiveness of microtubule-targeting agents will not only facilitate a better understanding of the mechanisms of acquired drug resistance but will also be amenable to therapeutic interventions. We discovered a novel microtubule associated protein “Matrin 3 (MATR3)” that is known to bind to RNA and play a critical role in RNA transport and RNA stabilization. Our results revealed that MATR3 acts as a potent tumor suppressor as it inhibits long-term growth, migration, invasion as well as tumor growth of triple negative breast cancer (TNBC) cells in vivo. We demonstrated that MATR3 overexpression induced cell cycle arrest and apoptosis in TNBC cells. Furthermore, analysis of breast cancer samples showed a significantly lower expression of MATR3 when compared to normal adjacent tissues. Importantly, our RNA immunoprecipitation (RIP)-seq analysis showed that MATR3 controls expression of several mitotic spindle organizing proteins by binding to their RNA. Interestingly, we found that these MATR3 regulated proteins were highly altered in breast cancer patients. In conclusion, we identified a novel RNA-binding protein that inhibits breast cancer growth and progression suppressor by regulating microtubule dynamics. Citation Format: Panneerdoss Subbarayalu, Subapriya Rajamanickam, Suryavathi Viswanadhapalli, Benjamin C. Onyeagucha, Vijay K. Eedunuri, Nicholas Dybdal-Hargreaves, Santosh Timilsina, Hima Bansal, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, John C. Herr, Susan L. Mooberry, Manjeet K. Rao. A novel microtubule associated RNA binding protein matrin 3 act as a tumor suppressor by regulating mitotic spindle organizing proteins in triple negative breast cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3658.