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Session: ePoster Monitor 2-Colon Cancer 1

eP270 - Role of Mitochondria in Regulation of Colorectal Cancer Progression

Sunday, June 2, 2024
10:39 AM – 10:44 AM ET, USA
Location: Baltimore Convention Center, Room 318-320

    ePoster Presenter(s)

  • Ashok Kumar, MBBS, MS, MCh, FRCS, FACS, FASCRS (he/him/his)

    Professor, Department of Surgical Gastroenterology
    Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, INDIA
    Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, INDIA
    Lucknow, Uttar Pradesh, India

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

    • Author(s)

  • SM

    Shashank Mathur, M.Tech (Biotechnology)

    PhD. student
    Sanjay Gandhi Post Graduate Institute of Medical Sciece
    Lucknow, Uttar Pradesh, India

    Disclosure information not submitted.

  • KS

    Kirti Saini, n/a

    Ph.D student
    SGPGIMS Lucknow
    Lucknow, Uttar Pradesh, India

    Disclosure information not submitted.

    • Senior Author(s)

  • LS

    Lokendra K. Sharma, PhD

    Associate Professor
    Department of Molecular Medicine and Biotechnology, SGPGIMS Lucknow
    Lucknow, Uttar Pradesh, India

    Disclosure information not submitted.

Purpose/Background: Mitochondria plays a crucial role in cancer proliferation and metastasis through bioenergetics and metabolic reprogramming. However, the regulation of mitochondria in colorectal cancer (CRC) remains unclear. In this preliminary study, we investigated mitochondrial turnover, mainly biogenesis and clearance, to understand its contribution in CRC metastasis.Methods/Interventions: Paired tissue from locally advanced CRC patients (Stage III, lymph node metastasis) and in vitro CRC cell lines with differences in metastatic potential (HCT116, HT 29) were used to analyze mitochondrial DNA content and gene/protein expression of markers of mitochondrial biogenesis (PGC1α, NRF1 and TFAM) and autophagy/mitophagy pathways (ATG14, P62, LC3B, P62 and Optineurin). mtDNA content and gene expression were analyzed by qPCR, and protein expression was analyzed by immunoblotting, and compared with their respective controls for significant differences.Results/Outcomes: The study was carried between July 2022 to September 2023 in 15 patients of CRC as a part of ongoing research on role of Mitochondrial Dynamic proteins in colorectal cancer. There were 7 male and 8 female patients with the mean age of 54.6 ± 12.2 years (median age 57.5 years). Analysis revealed that mtDNA content and biogenesis markers were significantly upregulated in tumor tissue and metastatic cells, indicating an increased requirement of mitochondria for metastatic progression. Interestingly, autophagy markers were found to be upregulated in both CRC tissues and metastatic CRC cells, the level of mitophagy markers remained unchanged or decreased, reinforcing the requirement of mitochondria in CRC. Furthermore, ongoing in vitro studies indicate that mitochondrial inhibition sensitizes highly metastatic cells to cell death.Conclusion/

Discussion: Overall, increased mitochondrial mtDNA content and biogenesis could be linked to increased mitochondrial functionality required for the metastatic progression of CRC. These findings may be useful in therapeutic targeting of mitochondria in developing effective combinations for the treatment of metastatic cancers. Further study on large sample size is required to validate these findings.