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ASO Author Reflections: ASCL2, a Marker of Dynamic Colon Stem Cell, Involved in Wnt Pathway Activation Reflects Anti-cancer Drug Resistance in Primary Colorectal Cancer

  • Toshimichi Tanaka
  • Keishi YamashitaEmail author
ASO Author Reflections

Past

A portion of colorectal cancer (CRC) is resistant to anticancer treatment. The molecular mechanisms involved in drug resistance must be clarified to develop new therapeutic strategies and biomarkers.

Present

We applied a phenylbutyrate administration model, previously used for exploration of genes involved in drug resistance in breast cancer and searched novel genes explaining drug resistance to CRC.1 In the current study, ASCL2 was significantly associated with resistance against phenylbutyrate, 5-FU, and radiotherapy.2 The regulation of ASCL2 may provide a clue for the molecular understanding of CRC treatment failure.

Future

Ascl2 is a marker of dynamic stem cell of goblet cells of the colorectal noncancerous mucosa. Recently, ASCL2 expression was mainly regulated by long noncoding RNA of WiNTRLINC1 in CRC, which is a direct target of Wnt pathways.3 Establishment of control of Wnt pathway, including WiNTRLNC1-ASCL2 axis, may greatly contribute to suppression of CRC from therapeutic point of view through understanding genetic linkage of normal stem cells to cancer occurrence in the future.

Notes

Disclosures

Toshimichi Tanaka and Keishi Yamashita have no conflicts of interest to disclose.

References

  1. 1.
    Kikuchi M, Yamashita K, Waraya M, et al. Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget. 2016;7:1741–53.CrossRefGoogle Scholar
  2. 2.
    Tanaka T, Kojima K, Yokota K, et al. Comprehensive genetic search to clarify the molecular mechanism of drug resistance identifies ASCL2-LEF1/TSPAN8 axis in colorectal cancer. Ann Surg Oncol. 2019;26:1401–11.CrossRefGoogle Scholar
  3. 3.
    Giakountis A, Moulos P, Zarkou V, et al. A positive regulatory loop between a Wnt-regulated non-coding RNA and ASCL2 controls intestinal stem cell fate. Cell Rep. 2016;15:2588–96.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  1. 1.Department of SurgeryKitasato University School of MedicineSagamiharaJapan
  2. 2.Epigenetic Treatment Research GroupChiyoda-ku, TokyoJapan
  3. 3.Division of Advanced Surgical Oncology, Department of Research and Development Center for New Medical FrontiersKitasato University School of MedicineSagamiharaJapan

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