M. Cecilia Caino, PhD

Assistant Professor


 
Cecilia Caino 3-2

Contact Information:

University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-South
12801 East 17th Ave
Aurora CO 80045

Phone: (303) 724-3528
Fax: (303) 724-3663
Office: RC1-South, L18-6124
 

Metastastic cancer remains incurable and invariably kills 90% of cancer patients. Despite significant progress in determining the molecular and biochemical determinants of the metastatic cascade, we still lack actionable targets for metastatic disease. Filling this gap, our lab focuses on understanding the importance of mitochondria biology in metastatic breast and prostate cancer.  Mitochondria are bioenergetic, biosynthetic, and signaling organelles that have been implicated in various aspects of tumorigenesis and therapy resistance.  Indeed, mitochondrial respiration has been linked to oncogene-dependent transformation, metabolic reprogramming, protein translation, tumor repopulation, cell motility and metastasis.  In this context, mitochondrial quality control mechanisms are emerging as drivers of metastasis and attractive therapeutic targets. 

 

Mitochondrial dynamics in cancer. A key mechanism by which tumors regulate mitochondrial functions are the collective processes of mitochondrial dynamics. Mitochondrial dynamics refers to spatiotemporal regulation of gross morphology, transport of organelles, inner membrane and cristae morphology, communication between adjacent mitochondria and contact with other organelles such as the endoplasmic reticulum. Tumor microenvironmental conditions (hypoxia, starvation and oxidative stress) exploit mitochondrial dynamics as adaptive mechanisms. In this context, the possibility that mitochondria trafficking might affect tumor biology is poorly studied. In a series of recent contributions, we show that tumor cells reposition mitochondria at subcellular sites of high energetic demands, thus powering up mechanisms of invasion and metastasis. Disparate stimuli, ranging from growth factor stimulation, to therapy resistance to hypoxic stress, led to the trafficking of energetically active mitochondria to the cortical cytoskeleton of tumor cells. In turn, regional energy production supported membrane lamellipodia dynamics and increased turnover of focal adhesion complexes. 

Deregulated mitochondrial trafficking fuels metastasis. The mitochondrial trafficking machinery had been previously studied in the context of neuronal cells, and many of the molecules were believed to be neuron-specific.  Recently, we identified the molecular motors and adaptors responsible for trafficking of mitochondria in tumor cells by a genome-wide shRNA screen. Syntaphilin (SNPH), the molecular brake anchoring mitochondria to microtubules, is broadly expressed in normal tissues and lost in most cancer types, including breast cancer. Higher levels of SNPH were associated with removal of mitochondria from the cortical cytoskeleton, impaired focal adhesion dynamics and inhibition of tumor cell invasion and metastasis. In patients, SNPH loss in tumors correlated with shortened patient survival. Conversely, positive regulators of mitochondrial trafficking, the mitochondrial Rho GTPases (Miro) 1 and 2, were overexpressed in patient cohorts and were associated with poorer prognosis. Our current goal are: (i) to  dissect the molecular mechanisms underlying mitochondrial trafficking in tumors, particularly in the context of hypoxic stress from the tumor microenvironment; (ii) to understand how rewiring of the mitochondrial network in tumors impacts cellular behaviors that drive progressive and lethal cancer; and (iii) to examine the contribution of the mitochondrial trafficking components (SNPH, Miro1/2 and Kinesin) to tumor cell invasion and metastatic dissemination. ​ 

Current Lab Members

First NameLast NameMiddle Initial DegreePosition
DillonBoulton BSGraduate Student
MadisonFurnish BSGraduate Student
VictoriaGenther BS/MSProfessional Research Assistant
DenisaGrofova MSGraduate Student

 

Alumni

First NameLast NameMiddle InitialDegreePosition
MitchellEllinwood BSCU Cancer Center Fellow
Sarah ConnorK.BSCancer Center Fellow

091521 #2b

Selected publications 2021

  1. Furnish M, Boulton DP, Genther V, Ellinwood ML, Romero L, Lucia MS, Cramer SD, Caino MC. “MIRO2 regulates prostate cancer cell growth via GCN1-dependent stress signaling”. bioRxiv May 21, 2021. https://www.biorxiv.org/content/10.1101/2021.05.20.444992v1.
  2. Furnish M, Caino MC. “Altered mitochondrial trafficking as a novel mechanism of cancer metastasis”. Cancer Rep. 2020 Feb;3(1):e1157. PMID: 32671955. Review.
  3. Williams M, Caino MC. “Mitochondrial Dynamics in Type 2 Diabetes and Cancer”. Front Endocrinol. 2018 Apr 27;9:211. doi: 10.3389/fendo.2018.00211. eCollection 2018. Review. PMID: 29755415. PMCID: PMC5934432.
    1. Caino MC, Seo JH, Wang Y, Rivadeneira DB, Gabrilovich DI, Kim ET, Weeraratna AT, Languino LR, Altieri DC.  “Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer”. J Clin Invest. 2017 Sep 11. pii: 93172. doi: 10.1172/JCI93172. PMID: 28891816. PMCID: PMC5617650.
    2. Caino MC, Seo JH, Aguinaldo A, Wait E, Bryant KG, Kossenkov AV, Hayden JE, Vaira V, Morotti A, Ferrero S, Bosari S, Gabrilovich DI, Languino LR, Cohen AR, Altieri DC. “A neuronal network of mitochondrial dynamics regulates metastasis”. Nat Commun 2016 7, 13730 doi: 10.1038/ncomms13730. PMID: 27991488. PMCID: PMC5187409.
    3. Caino MC and Altieri DC. “Molecular Pathways: Mitochondrial Reprogramming in Tumor Progression and Therapy”. Clin Cancer Res. 2016 Feb 1;22(3):540-5. doi: 10.1158/1078-0432.CCR-15-0460. PMID: 26660517. PMCID: PMC4738153.
    4. Caino MC, Ghosh JC, Chae YC, Vaira V, Rivadeneira DB, Faversani A, Rampini P, Kossenkov AV, Aird KM, Zhang R, Webster MR, Weeraratna AT, Bosari S, Languino LR, Altieri DC. et al. “PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion”. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8638-43. PMID: 26124089. PMCID: PMC4507184.
    5. Caino MC, Chae YC, Vaira V, Ferrero S, Nosotti M, Martin NM, Weeraratna A, O’Connell M, Jernigan D, Fatatis A, Languino LR, Bosari S, Altieri DC. “Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells”. J Clin Invest. 2013 Jul;123(7):2907-20. PMID:23921130. PMCID: PMC3998961.
    6.  

      For a complete list visit:

      http://www.ncbi.nlm.nih.gov/sites/myncbi/maria.caino.1/bibliography/42191957/public/?sort=date&direction=descending

     

    7/26/21 – Ceci is promoted to Full Member of the Molecular and Cellular Oncology Program of the University of Colorado Cancer Center.

     

    7/15/21 – The lab is looking to expand! Postdoc applicants and rotation students welcome!

     

    7/1/21 – The lab is awarded a DoD CDMRP Idea Development award to study a novel mitochondrial signaling axis for therapeutic gain in prostate cancer.

     

    6/15/21 – The lab is awarded a NIGMS Maximizing Research Investigator Award to study mitochondrial dynamics in mammalian cells.

     

    5/25/21 – Sarah Kate joins the lab for her summer Cancer Research Experience for Undergraduates. Welcome!

     

    5/24/21 – Denisa joins the lab as a student research assistant. Welcome Denisa!

     

    4/27/21 – Ceci’s studies on metastatic prostate cancer are featured in the University of Colorado Cancer Center’s newsroom: https://news.cuanschutz.edu/cancer-center/dod-grants-investigate-metastasis

     

    4/21/21 – Madison’s paper characterizing a novel signaling axis important for prostate cancer growth is posted to bioRxiv. You can read the pre-print here:https://www.biorxiv.org/content/10.1101/2021.05.20.444992v1. Congratulations to Madison, Dillon and Victoria for this achievement!

     

    1/11/21 – Dillon receives a best poster award at the 35th Annual Student Research Forum. Congratulations!

     

    10/16/20 – Dillon receives a best poster award at the Pharmacology Student Research Day. Congratulations!

     

    8/17/20 – Ceci is interviewed about her research in mitochondrial dynamics by the Cancer Center: https://news.cuanschutz.edu/cancer-center/qa-a-conversation-with-cecilia-caino-phd

     

    7/30/20 – Dillon passed his Comprehensive Exam and is now an official PhD candidate!

     

    6/1/20 – The lab reopens with limited capacity.

     

    3/16/20 – The campus closes during the COVID pandemic.